383 research outputs found

    Pine cone scale-inspired motile origami

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    Stimuli-sensitive hydrogels have received attention because of their potential applications in various fields. Stimuli-directed motion offers many practical applications, such as in drug delivery systems and actuators. Directed motion of asymmetric hydrogels has long been designed; however, few studies have investigated the motion control of symmetric hydrogels. We designed a pine cone scale-inspired movable temperature-sensitive symmetric hydrogel that contains Fe3O4. Alignment of Fe3O4 along the magnetic force is key in motion control in which Fe3O4 acts like fibers in a pine cone scale. Although a homogeneous temperature-sensitive hydrogel cannot respond to a temperature gradient, the Fe3O4-containing hydrogel demonstrates considerable bending motion. Varying degrees and directions of motion are easily facilitated by controlling the amount and alignment angle of the Fe3O4. The shape of the hydrogel layer also influences the morphological structure. This study introduced facile and low-cost methods to control various bending motions. These results can be applied to many fields of engineering, including industrial engineering.111Ysciescopu

    Synaptic tagging and capture in the living rat

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    In isolated hippocampal slices, decaying long-term potentiation can be stabilized and converted to late long-term potentiation lasting many hours, by prior or subsequent strong high-frequency tetanization of an independent input to a common population of neurons—a phenomenon known as ‘synaptic tagging and capture’. Here we show that the same phenomenon occurs in the intact rat. Late long-term potentiation can be induced in CA1 during the inhibition of protein synthesis if an independent input is strongly tetanized beforehand. Conversely, declining early long-term potentiation induced by weak tetanization can be converted into lasting late long-term potentiation by subsequent strong tetanization of a separate input. These findings indicate that synaptic tagging and capture is not limited to in vitro preparations; the past and future activity of neurons has a critical role in determining the persistence of synaptic changes in the living animal, thus providing a bridge between cellular studies of protein synthesis-dependent synaptic potentiation and behavioural studies of memory persistence

    Identifying Predictive Biomarkers of Response in Patients With Rheumatoid Arthritis Treated With Adalimumab Using Machine Learning Analysis of Whole-Blood Transcriptomics Data

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    \ua9 2025 The Author(s). Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology. Objective: Tumornecrosis factor inhibitors (TNFi) have significantly improved rheumatoid arthritis (RA) management, yet variability in patient response remains a substantial challenge, with approximately 40% of patients discontinuing TNFi due to nonresponse or adverse effects. This study aimed to identify biomarkers predictive of adalimumab treatment response using whole-blood transcriptomics, leveraging machine learning models for data mining observed by targeted statistical analysis. Methods: A cohort of patients with RA starting TNFi therapy (n = 100) was assessed for treatment response at 6 months, with RNA sequencing performed on baseline (pretreatment) and 3-month follow-up samples. Machine learning classifiers were built to identify predictive biomarkers for treatment outcomes. This was observed by a network analysis on the biomarkers to elucidate the most influential biomarker, which was subsequently confirmed through survival analysis. Results: Differential gene expression analysis in 97 samples passing quality control identified 84 genes associated with treatment response. Random forest classifiers achieved high predictive accuracy with area under the receiver operating characteristic curves up to 0.86, identifying genes contributing to treatment outcomes. Network analysis further elucidated gene interactions, highlighting marginal zone B And B1 cell–specific protein 1 (MZB1) as a novel biomarker not captured by machine learning alone. MZB1\u27s role in B cell development and antibody production was associated with antidrug antibody formation, impacting treatment efficacy. Conclusion: This study advances the understanding of transcriptomic alterations in RA treatment and enhances our understanding of treatment response mechanisms. Although the gene signatures identified require independent replication, the study serves as a starting point to pave the way for personalized therapeutic strategies in patients commencing TNFi therapy in RA

    Cytoplasmic Polyadenylation Element Binding Protein Deficiency Stimulates PTEN and Stat3 mRNA Translation and Induces Hepatic Insulin Resistance

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    The cytoplasmic polyadenylation element binding protein CPEB1 (CPEB) regulates germ cell development, synaptic plasticity, and cellular senescence. A microarray analysis of mRNAs regulated by CPEB unexpectedly showed that several encoded proteins are involved in insulin signaling. An investigation of Cpeb1 knockout mice revealed that the expression of two particular negative regulators of insulin action, PTEN and Stat3, were aberrantly increased. Insulin signaling to Akt was attenuated in livers of CPEB–deficient mice, suggesting that they might be defective in regulating glucose homeostasis. Indeed, when the Cpeb1 knockout mice were fed a high-fat diet, their livers became insulin-resistant. Analysis of HepG2 cells, a human liver cell line, depleted of CPEB demonstrated that this protein directly regulates the translation of PTEN and Stat3 mRNAs. Our results show that CPEB regulated translation is a key process involved in insulin signaling

    Genome-wide and Ordered-Subset linkage analyses provide support for autism loci on 17q and 19p with evidence of phenotypic and interlocus genetic correlates

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    BACKGROUND: Autism is a neurobehavioral spectrum of phenotypes characterized by deficits in the development of language and social relationships and patterns of repetitive, rigid and compulsive behaviors. Twin and family studies point to a significant genetic etiology, and several groups have performed genomic linkage screens to identify susceptibility loci. METHODS: We performed a genome-wide linkage screen in 158 combined Tufts, Vanderbilt and AGRE (Autism Genetics Research Exchange) multiplex autism families using parametric and nonparametric methods with a categorical autism diagnosis to identify loci of main effect. Hypothesizing interdependence of genetic risk factors prompted us to perform exploratory studies applying the Ordered-Subset Analysis (OSA) approach using LOD scores as the trait covariate for ranking families. We employed OSA to test for interlocus correlations between loci with LOD scores ≥1.5, and empirically determined significance of linkage in optimal OSA subsets using permutation testing. Exploring phenotypic correlates as the basis for linkage increases involved comparison of mean scores for quantitative trait-based subsets of autism between optimal subsets and the remaining families. RESULTS: A genome-wide screen for autism loci identified the best evidence for linkage to 17q11.2 and 19p13, with maximum multipoint heterogeneity LOD scores of 2.9 and 2.6, respectively. Suggestive linkage (LOD scores ≥1.5) at other loci included 3p, 6q, 7q, 12p, and 16p. OSA revealed positive correlations of linkage between the 19p locus and 17q, between 19p and 6q, and between 7q and 5p. While potential phenotypic correlates for these findings were not identified for the chromosome 7/5 combination, differences indicating more rapid achievement of "developmental milestones" was apparent in the chromosome 19 OSA-defined subsets for 17q and 6q. OSA was used to test the hypothesis that 19p linkage involved more rapid achievement of these milestones and it revealed significantly increased LOD* scores at 19p13. CONCLUSIONS: Our results further support 19p13 as harboring an autism susceptibility locus, confirm other linkage findings at 17q11.2, and demonstrate the need to analyze more discreet trait-based subsets of complex phenotypes to improve ability to detect genetic effects

    Transcriptome profiling of immune responses to cardiomyopathy syndrome (CMS) in Atlantic salmon

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    <p>Abstract</p> <p>Background</p> <p>Cardiomyopathy syndrome (CMS) is a disease associated with severe myocarditis primarily in adult farmed Atlantic salmon (<it>Salmo salar </it>L.), caused by a double-stranded RNA virus named piscine myocarditis virus (PMCV) with structural similarities to the <it>Totiviridae </it>family. Here we present the first characterisation of host immune responses to CMS assessed by microarray transcriptome profiling.</p> <p>Results</p> <p>Unvaccinated farmed Atlantic salmon post-smolts were infected by intraperitoneal injection of PMCV and developed cardiac pathology consistent with CMS. From analysis of heart samples at several time points and different tissues at early and clinical stages by oligonucleotide microarrays (SIQ2.0 chip), six gene sets representing a broad range of immune responses were identified, showing significant temporal and spatial regulation. Histopathological examination of cardiac tissue showed myocardial lesions from 6 weeks post infection (wpi) that peaked at 8-9 wpi and was followed by a recovery. Viral RNA was detected in all organs from 4 wpi suggesting a broad tissue tropism. High correlation between viral load and cardiac histopathology score suggested that cytopathic effect of infection was a major determinant of the myocardial changes. Strong and systemic induction of antiviral and IFN-dependent genes from 2 wpi that levelled off during infection, was followed by a biphasic activation of pathways for B cells and MHC antigen presentation, both peaking at clinical pathology. This was preceded by a distinct cardiac activation of complement at 6 wpi, suggesting a complement-dependent activation of humoral Ab-responses. Peak of cardiac pathology and viral load coincided with cardiac-specific upregulation of T cell response genes and splenic induction of complement genes. Preceding the reduction in viral load and pathology, these responses were probably important for viral clearance and recovery.</p> <p>Conclusions</p> <p>By comparative analysis of gene expression, histology and viral load, the temporal and spatial regulation of immune responses were characterised and novel immune genes identified, ultimately leading to a more complete understanding of host-virus responses and pathology and protection in Atlantic salmon during CMS.</p
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