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Xue, X.

Publications and source records attributed to Xue, X..

57 records · Page 4Linked to original sources

The Creative Mind: Blending Oxytocinergic, Dopaminergic and Personality

In a fast-changing world, creative thinking (CT) is an extraordinary currency. Oxytocin (OT) is associated with CT and release of OT depends on ADP ribosyl-cyclases (CD38 and CD157). Moreover, CT as well as OTs mechanism of action are mediated via central dopaminergic pathways. Consequently, we evaluate the roles of CD38, CD157, dopamine receptor D2 (DRD2) and catechol-O-methyltransferase (COMT) peripheral gene expression in CT. Two principal domains of CT, divergent thinking and insight solving problems, were assessed using validated behavioral assessments. To facilitate discriminant validity, two established correlates of CT, trait Openness and fluid intelligence as well as age and sex were included in the regression model. In women, significant main effects (p<0.01) were positively associated with the expression CD38, CD15, and their interaction CD38 x CD157 controlling for Openness, fluid intelligence and age. Subsequent analysis on the subscale-level revealed significant main effects for CD157 and CD38 x CD157 in men specifically for divergent thinking. In women, significant (p<0.01) results are also observed for dopaminergic expression (DRD2, COMT, DRD2 x COMT). The full model (oxytocinergic and dopaminergic gene expressions, Openness, and fluid intelligence) explains a sizable 39% of the variance in females. Significant main effects are observed for CD38, CD157, DRD2 and COMT as well as their interactions (CD38xCD157 and DRD2xCOMT). In conclusion, we show that oxytocinergic and dopaminergic gene expression contribute significantly to the complex CT phenotype suggesting the notion that the perspective gained from examining the peripheral transcriptome meaningfully adds to understanding the landscape of creative thinking.\n\nSignificance StatementCreative thinking (CT) is a powerful driving force galvanizing progress and civilization. Towards better understanding the neurobiology of CT, we implement a gene expression strategy that is considered to capture not only genomic elements but also environmental signatures. We employ laboratory measures of CT (alternative uses test and insight problem solving), controlling for fluid intelligence and the personality trait of Openness. We focus on oxytocinergic and dopaminergic genes that contribute to the molecular architecture of CT. Oxytocinergic and dopaminergic gene expression significantly explains a robust 39% of the variance in CT. Notably, this study demonstrates the potential of the peripheral transcriptome towards tracing gene pathways underlying some complex cognitive behaviors such as creative thinking.

neuroscience↗

The innate immune DNA sensor cGAS is a negative regulator of DNA repair hence promotes genome instability and cell death

Stringent regulation of DNA repair is essential for organismal integrity, but the mechanisms are not fully understood. Cyclic cGMP-AMP synthase (cGAS), the DNA sensor that alerts the innate immune system to the presence of foreign or damaged self-DNA in the cytoplasm is critical for the outcome of infections, inflammatory diseases and cancer. Besides this cytoplasmic function as an innate immune sensor, whether cGAS fulfills other biological roles remains unknown. Here we report that cGAS has a distinct role in the nucleus: it inhibits homologous recombination DNA repair (HR) thereby promoting genome instability and associated micronuclear generation and mitotic death. We show that cGAS-mediated inhibition of HR requires its DNA binding and oligomerization but not its catalytic activity or the downstream innate immune signaling events. Mechanistically, we show that cGAS impede RAD51-mediated DNA strand invasion, a key step in HR. These results uncover a new function of cGAS relevant for understanding its involvement in genome instability- associated disorders.

cell biology↗

Identification, Isolation, and Characterization of Human LGR5-positive Colon Adenoma Cells

The intestine is maintained by stem cells located at the base of crypts and distinguished by the expression of LGR5. Genetically engineered mouse models have provided a wealth of information about intestinal stem cells, while less is known about human intestinal stem cells due to difficulty detecting and isolating these cells. We established an organoid repository from patient-derived adenomas, adenocarcinomas, and normal colon, which we analyzed for variants in 71 colorectal cancer (CRC) associated genes. Normal and neoplastic colon tissue organoids were analyzed by immunohistochemistry and fluorescent-activated cell sorting for LGR5. LGR5-positive cells were isolated from 4 adenoma organoid lines and were subjected to RNA-sequencing. We found that LGR5 expression in the epithelium and stroma was associated with tumor stage, and by integrating functional experiments with LGR5-sorted cell RNA-seq data from adenoma and normal organoids, we found correlations between LGR5 and CRC- specific genes, including DKK4 (dickkopf WNT signaling pathway inhibitor 4) and SMOC2 (SPARC related modular calcium binding 2). Collectively, this work provides resources, methods and new markers to isolate and study stem cells in human tissue homeostasis and carcinogenesis.

cancer biology↗