1,524 research outputs found

    Cells derived from iPSC can be immunogenic — Yes or No?

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    The induced pluripotent stem cells (iPSCs), derived by ectopic expression of reprogramming factors in somatic cells, can potentially provide unlimited autologous cells for regenerative medicine. In theory, the autologous cells derived from patient iPSCs should be immune tolerant by the host without any immune rejections. However, our recent studies have found that even syngeneic iPSC-derived cells can be immunogenic in syngeneic hosts by using a teratoma transplantation model (Nature 474:212–215, 2011). Recently two research groups differentiated the iPSCs into different germ layers or cells, transplanted those cells to the syngeneic hosts, and evaluated the immunogenicity of those cells. Both of the two studies support our conclusions that some certain but not all tissues derived from iPSCs can be immunogenic, although they claimed either “negligible” or “lack of” immunogenicity in iPSC derivatives (Nature 494:100–104, 2013; Cell Stem Cell 12:407–412, 2013). To test the immunogenicity of clinically valuable cells differentiated from human iPSCs are emergently required for translation of iPSC technology to clinics

    Histone Lysine Methyltransferase SDG8 Is Involved in Brassinosteroid-Regulated Gene Expression in Arabidopsis thaliana

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    Citation: Wang, X., Chen, J., Xie, Z., Liu, S., Nolan, T., Ye, H., et al. (2014). Histone lysine methyltransferase SDG8 is involved in brassinosteroid- regulated gene expression in arabidopsis thaliana.The plant steroid hormones, brassinosteroids (BRs), play important roles in plant growth, development and responses to environmental stresses. BRs signal through receptors localized to the plasma membrane and other signaling components to regulate the BES1/BZR1 family of transcription factors, which modulates the expression of 4,000-5,000 genes. How BES1/BZR1 and their interacting proteins function to regulate the large number of genes are not completely understood. Here we report that histone lysine methyltransferase SDG8, implicated in Histone 3 lysine 36 di- and tri-methylation (H3K36me2 and me3), is involved in BR-regulated gene expression. BES1 interacts with SDG8, directly or indirectly through IWS1, a transcription elongation factor involved in BR-regulated gene expression. The knockout mutant sdg8 displays a reduced growth phenotype with compromised BR responses. Global gene expression studies demonstrated that SDG8 plays a major role in BR-regulated gene expression as more than half of BR-regulated genes are differentially affected in sdg8 mutant. A Chromatin Immunoprecipitation (ChIP) experiment showed that H3K36me3 is reduced in BR-regulated genes in the sdg8 mutant. Based on these results, we propose that SDG8 plays an essential role in mediating BR-regulated gene expression. Our results thus reveal a major mechanism by which histone modifications dictate hormonal regulation of gene expression

    Scallop: A Language for Neurosymbolic Programming

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    We present Scallop, a language which combines the benefits of deep learning and logical reasoning. Scallop enables users to write a wide range of neurosymbolic applications and train them in a data- and compute-efficient manner. It achieves these goals through three key features: 1) a flexible symbolic representation that is based on the relational data model; 2) a declarative logic programming language that is based on Datalog and supports recursion, aggregation, and negation; and 3) a framework for automatic and efficient differentiable reasoning that is based on the theory of provenance semirings. We evaluate Scallop on a suite of eight neurosymbolic applications from the literature. Our evaluation demonstrates that Scallop is capable of expressing algorithmic reasoning in diverse and challenging AI tasks, provides a succinct interface for machine learning programmers to integrate logical domain knowledge, and yields solutions that are comparable or superior to state-of-the-art models in terms of accuracy. Furthermore, Scallop's solutions outperform these models in aspects such as runtime and data efficiency, interpretability, and generalizability

    Advances in the study of Ophiopogon japonicus polysaccharides: structural characterization, bioactivity and gut microbiota modulation regulation

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    Ophiopogon japonicus polysaccharides (OJPS), the principal bioactive constituents isolated from Ophiopogon japonicus, demonstrate substantial physiological efficacy. OJPS is characterized by a high molecular weight, typically ranging from 2.48 to 324.7 kDa. Emerging evidence indicates that OJPS modulates the composition and structural organization of the gut microbiota, thereby maintaining intestinal barrier integrity and enhancing both gastrointestinal and systemic homeostasis. Moreover, OJPS and its metabolic derivatives engage in dynamic interactions with microbial communities, mediating cellular signaling cascades and endocrine regulation to elicit hypoglycemic effects. Despite these findings, comprehensive analyses of OJPS extraction and purification methodologies, structural elucidation, biological functionalities, and mechanistic insights into its crosstalk with the gut microbiota remain scarce. This review systematically synthesizes contemporary knowledge pertaining to the preparation, structural attributes, bioactivity, and mechanistic underpinnings of OJPS, with particular emphasis on its dual regulatory role in host physiology and gut microbial ecology

    Case Report: Kyrieleis plaques in an unusual Behcet's disease uveitis

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    Kyrieleis plaques are a rare retinal manifestation that has rarely been reported in Behcet's disease uveitis. We report the case of a 41-year-old man who presented with Behçet's disease uveitis combined with central serous chorioretinopathy. Laboratory studies showed positive for human leukocyte antigen B51. Polymerase chain reaction analysis of aqueous humor excluded infectious uveitis. Kyrieleis plaques were observed in the bilateral retinal arteries. These plaques persisted in both eyes after half a year of immunosuppressive treatments. Kyrieleis plaques are not limited to infectious uveitis; they can also be associated with Behçet's disease uveitis

    LASER: A Neuro-Symbolic Framework for Learning Spatial-Temporal Scene Graphs with Weak Supervision

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    We propose LASER, a neuro-symbolic approach to learn semantic video representations that capture rich spatial and temporal properties in video data by leveraging high-level logic specifications. In particular, we formulate the problem in terms of alignment between raw videos and spatio-temporal logic specifications. The alignment algorithm leverages a differentiable symbolic reasoner and a combination of contrastive, temporal, and semantics losses. It effectively and efficiently trains low-level perception models to extract fine-grained video representation in the form of a spatio-temporal scene graph that conforms to the desired high-level specification. In doing so, we explore a novel methodology that weakly supervises the learning of video semantic representations through logic specifications. We evaluate our method on two datasets with rich spatial and temporal specifications: 20BN-Something-Something and MUGEN. We demonstrate that our method learns better fine-grained video semantics than existing baselines
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