Function annotation of hepatic retinoid x receptor α based on genome-wide DNA binding and transcriptome profiling.

BackgroundRetinoid x receptor α (RXRα) is abundantly expressed in the liver and is essential for the function of other nuclear receptors. Using chromatin immunoprecipitation sequencing and mRNA profiling data generated from wild type and RXRα-null mouse livers, the current study identifies the bona-fide hepatic RXRα targets and biological pathways. In addition, based on binding and motif analysis, the molecular mechanism by which RXRα regulates hepatic genes is elucidated in a high-throughput manner.Principal findingsClose to 80% of hepatic expressed genes were bound by RXRα, while 16% were expressed in an RXRα-dependent manner. Motif analysis predicted direct repeat with a spacer of one nucleotide as the most prevalent RXRα binding site. Many of the 500 strongest binding motifs overlapped with the binding motif of specific protein 1. Biological functional analysis of RXRα-dependent genes revealed that hepatic RXRα deficiency mainly resulted in up-regulation of steroid and cholesterol biosynthesis-related genes and down-regulation of translation- as well as anti-apoptosis-related genes. Furthermore, RXRα bound to many genes that encode nuclear receptors and their cofactors suggesting the central role of RXRα in regulating nuclear receptor-mediated pathways.ConclusionsThis study establishes the relationship between RXRα DNA binding and hepatic gene expression. RXRα binds extensively to the mouse genome. However, DNA binding does not necessarily affect the basal mRNA level. In addition to metabolism, RXRα dictates the expression of genes that regulate RNA processing, translation, and protein folding illustrating the novel roles of hepatic RXRα in post-transcriptional regulation

Two dimensional vertex-decorated Lieb lattice with exact mobility edges and robust flat bands

The mobility edge (ME) that marks the energy separating extended and localized states is a central concept in understanding the metal-insulator transition induced by disordered or quasiperiodic potentials. MEs have been extensively studied in three dimensional disorder systems and one-dimensional quasiperiodic systems. However, the studies of MEs in two dimensional (2D) systems are rare. Here we propose a class of 2D vertex-decorated Lieb lattice models with quasiperiodic potentials only acting on the vertices of a (extended) Lieb lattice. By mapping these models to the 2D Aubry-Andr\'{e} model, we obtain exact expressions of MEs and the localization lengths of localized states, and further demonstrate that the flat bands remain unaffected by the quasiperiodic potentials. Finally, we propose a highly feasible scheme to experimentally realize our model in a quantum dot array. Our results open the door to studying and realizing exact MEs and robust flat bands in 2D systems

5-(2,3,4,5,6-Penta­fluoro­phen­yl)-1,3,4-thia­diazol-2-amine

The title compound, C8H2F5N3S, was synthesized by the reaction of perfluoro­benzoic acid and thio­semicarbazide. The dihedral angle between the thia­diazole and perfluoro­phenyl ring is 35.41 (6)°. In the crystal, inter­molecular N—H⋯N hydrogen bonds link the mol­ecules, forming a three-dimensional network

(E)-N-(4-Chloro­benzyl­idene)-5-(4-methyl­phen­yl)-1,3,4-thia­diazol-2-amine

The title compound, C16H12ClN3S, was synthesized by the reaction of 5-(4-methyl­phen­yl)-1,3,4-thia­diazol-2-amine and 4-chloro­benzaldehyde. The thia­diazole ring is essentially planar with mean deviation of 0.0042 Å

KG-BART: Knowledge Graph-Augmented BART for Generative Commonsense Reasoning

Generative commonsense reasoning which aims to empower machines to generate sentences with the capacity of reasoning over a set of concepts is a critical bottleneck for text generation. Even the state-of-the-art pre-trained language generation models struggle at this task and often produce implausible and anomalous sentences. One reason is that they rarely consider incorporating the knowledge graph which can provide rich relational information among the commonsense concepts. To promote the ability of commonsense reasoning for text generation, we propose a novel knowledge graph augmented pre-trained language generation model KG-BART, which encompasses the complex relations of concepts through the knowledge graph and produces more logical and natural sentences as output. Moreover, KG-BART can leverage the graph attention to aggregate the rich concept semantics that enhances the model generalization on unseen concept sets. Experiments on benchmark CommonGen dataset verify the effectiveness of our proposed approach by comparing with several strong pre-trained language generation models, particularly KG-BART outperforms BART by 5.80, 4.60, in terms of BLEU-3, 4. Moreover, we also show that the generated context by our model can work as background scenarios to benefit downstream commonsense QA tasks.Comment: 10 pages, 7 figures, Appear in AAAI 202

Hepatocyte RXRalpha deficiency in matured and aged mice: impact on the expression of cancer-related hepatic genes in a gender-specific manner

<p>Abstract</p> <p>Background</p> <p>The occurrence of liver cancer is higher in males than in females, and the incidence increases during aging. Signaling pathways regulated by retinoid × receptor α (RXRα) are involved in hepatocellular carcinogenesis. The phenotype of hepatocyte RXRα deficient mice is different between genders. To explore the impact of hepatocyte RXRα deficiency on gender-dependent hepatic gene expression, we compared the expression profiles of cancer-related genes in 6 and 24 month old male and female mice.</p> <p>Results</p> <p>In 6 month old mice, male mutant mice showed more cancer-related genes with alteration in mRNA levels than females did (195 vs. 60). In aged mice (24 month), female mutant mice showed greater deviation in mRNA expression levels of cancer-related genes than their male counterparts (149 vs. 82). The genes were classified into five categories according to their role in carcinogenesis: apoptosis, metastasis, cell growth, stress, and immune respnse. In each category, dependent upon age and gender, the genes as well as the number of genes with altered mRNA levels due to RXRα deficiency varies.</p> <p>Conclusion</p> <p>The change in hepatic cancer-related gene expression profiles due to RXRα deficiency was gender- and age-dependent. The alteration of mRNA levels of cancer-related genes implied that aberrant RXRα signaling could potentially increase the risk of liver cancer and that retinoid signaling might contribute to gender- and age-associated liver cancer incidence.</p

12β,14-Dihy­droxy-3-oxo-5β,20(22)-cardenolide monohydrate

The title compound, digoxigenone, C23H30O5·H2O, was biotransformed from digoxigenin. In the crystal, inter­molecular O—H⋯O hydrogen bonds contribute to the formation of a three-dimensional supra­molecular structure. The title compound has three fused six-membered rings (A,B,C) and two non-fused five-membered rings (D,E). As in other structures, compound nucleus has a cis-trans-cis conformation for the A-B,B-C,C-D ring junctions with rings A, B and C exhibiting chair conformations