ROLE OF P300 ZZ DOMAIN IN CHROMATIN ASSOCIATION AND HISTONE ACETYLATION

Transcription is strictly regulated by numerous factors including transcription coactivators. The p300 protein and its close paralogue CREB-binding protein (CREBBP, aka CBP) are well-known transcriptional coactivators that have intrinsic lysine acetyltransferase activity. The functions of p300/CBP largely rely on their capabilities to bind to chromatin and to acetylate the histone substrates. However, the molecular mechanisms underlying the regulation of these processes are not fully understood. Through combination of various biochemical, biophysical and molecular approaches, we show that the ZZ-type zinc finger (ZZ) domain of p300 functions as a histone reader that specifically binds the N-terminal tail of histone H3. Crystal structure of p300 ZZ in complex with the H3 peptide reveals that the ZZ domain adopts a negatively charged cavity to anchor Ala1 and Arg2 of H3. The ZZ-H3 interaction is not sensitive to common post-translational modifications, such as methylation or acetylation, on the H3 tail. Both in vitro and cell-based assays reveal that p300 ZZ domain, together with bromodomain (BRD), is important in recruiting p300 to chromatin. As a module adjacent to the histone acetyltransferase (HAT) domain, ZZ domain is also required for efficient histone acetylation by HAT. The recognition of histone H3 by the ZZ domain selectively promotes p300-dependent acetylation specifically on histone H3K27 and H3K18, whereas the acetyllysine binding activity of BRD is required for acetylation of virtually all lysine residues in H3 and H4 tails. p300/CBP are frequently mutated or dysregulated in many human diseases including cancer. We found that p300 is overexpressed in small cell lung cancer (SCLC), the most aggressive subtype of lung cancer. By CRISPR/Cas9-mediated gene manipulation, we found that p300 depletion impedes proliferation of human and mouse SCLC cells whereas CBP depletion has little or no effect. Depletion of p300 reduces the expression of critical oncogenes such as the MYC family genes, indicating that p300 promotes SCLC cell growth by sustaining oncogene expression. In summary, we identified the ZZ domain of p300 as a novel histone H3 reader that is critical for the chromatin association and enzymatic activity of p300. Recognition of H3 by ZZ domain is important to the functions of p300 in human cancer

ArtGPT-4: Artistic Vision-Language Understanding with Adapter-enhanced MiniGPT-4

In recent years, large language models (LLMs) have made significant progress in natural language processing (NLP), with models like ChatGPT and GPT-4 achieving impressive capabilities in various linguistic tasks. However, training models on such a large scale is challenging, and finding datasets that match the model's scale is often difficult. Fine-tuning and training models with fewer parameters using novel methods have emerged as promising approaches to overcome these challenges. One such model is MiniGPT-4, which achieves comparable vision-language understanding to GPT-4 by leveraging novel pre-training models and innovative training strategies. However, the model still faces some challenges in image understanding, particularly in artistic pictures. A novel multimodal model called ArtGPT-4 has been proposed to address these limitations. ArtGPT-4 was trained on image-text pairs using a Tesla A100 device in just 2 hours, using only about 200 GB of data. The model can depict images with an artistic flair and generate visual code, including aesthetically pleasing HTML/CSS web pages. Furthermore, the article proposes novel benchmarks for evaluating the performance of vision-language models. In the subsequent evaluation methods, ArtGPT-4 scored more than 1 point higher than the current \textbf{state-of-the-art} model and was only 0.25 points lower than artists on a 6-point scale. Our code and pre-trained model are available at \url{https://huggingface.co/Tyrannosaurus/ArtGPT-4}.Comment: 16 page

Polymorphism in Growth Hormone Gene and its Association with Growth Traits in Siniperca chuatsi

Growth hormone (GH) is a candidate gene for growth traits in fish. In this study, we assessed associations between single nucleotide polymorphisms (SNPs) in GH gene with growth traits in 357 Siniperca chuatsi individuals using high-resolution melting. Two SNPs were identified in GH gene, with one mutation in exon 5 (g.5045T>C), and one mutation in intron 5 (g.5234T>G). The corrections analysis of SNPs with the four growth traits was carried out using General Linear Model (GLM) estimation. Results showed that both of them were significantly associated with growth performance in S. chuatsi. For g.5234T>G, it was significantly associated with body weight (P＜0.01), body length (P＜0.05), body depth (P＜0.01), and body width (P＜0.01), and the individuals of genotype GG grew faster than those of genotypes TT and TG (P＜0.05). A further diplotype-trait association analysis confirmed that in fish with H3H2 (TC-GG) diplotype body weight, body length, and body width was greater than in those with other diplotypes (P＜0.05). These results demonstrated GH gene SNPs could be used as potential genetic markers in future marker assisted selection of S. chuatsi

Weldable and closed-loop recyclable monolithic dynamic covalent polymer aerogels

Owing to their low density, high porosity and unique micro-nanostructures, aerogels are attractive for application in various fields; however, they suffer from shrinkage and/or cracking during preparation, mechanical brittleness, low production efficiency and non-degradation. Herein, we introduce the concept of dynamic covalent polymer chemistry to produce a new class of aerogels&mdash;referred to as DCPAs. The resulting lightweight DCPAs have the potential to be prepared on a large scale and feature high porosity (90.7%&ndash;91.3%), large degrees of compression (80% strain) and bending (diametral deflection of 30 mm) without any cracks, as well as considerable tensile properties (an elongation with a break at 32.7%). In addition, the DCPAs showcase the emergent characteristics of weldability, repairability, degradability and closed-loop recyclability that are highly desirable for providing versatile material platforms, though hardly achieved by traditional aerogels. Taking advantage of their robust porous structures, we demonstrate the potential of DCPAs for applications in thermal insulation and emulsion separation. These findings reveal that the dynamic covalent bond strategy would be generalized for the production of a new generation of aerogels with customized features for functioning in the field of intelligent and sustainable materials. &nbsp;</p

Epithelial-to-mesenchymal transition drives a pro-metastatic Golgi compaction process through scaffolding protein PAQR11

Tumor cells gain metastatic capacity through a Golgi phosphoprotein 3-dependent (GOLPH3-dependent) Golgi membrane dispersal process that drives the budding and transport of secretory vesicles. Whether Golgi dispersal underlies the prometastatic vesicular trafficking that is associated with epithelial-to-mesenchymal transition (EMT) remains unclear. Here, we have shown that, rather than causing Golgi dispersal, EMT led to the formation of compact Golgi organelles with improved ribbon linking and cisternal stacking. Ectopic expression of the EMT-activating transcription factor ZEB1 stimulated Golgi compaction and relieved microRNA-mediated repression of the Golgi scaffolding protein PAQR11. Depletion of PAQR11 dispersed Golgi organelles and impaired anterograde vesicle transport to the plasma membrane as well as retrograde vesicle tethering to the Golgi. The N-terminal scaffolding domain of PAQR11 was associated with key regulators of Golgi compaction and vesicle transport in pull-down assays and was required to reconstitute Golgi compaction in PAQR11-deficient tumor cells. Finally, high PAQR11 levels were correlated with EMT and shorter survival in human cancers, and PAQR11 was found to be essential for tumor cell migration and metastasis in EMT-driven lung adenocarcinoma models. We conclude that EMT initiates a PAQR11-mediated Golgi compaction process that drives metastasis

The Sihailongwan Maar Lake, northeastern China as a candidate Global Boundary Stratotype Section and Point for the Anthropocene Series

Sihailongwan Maar Lake, located in Northeast China, is a candidate Global boundary Stratotype Section and Point (GSSP) for demarcation of the Anthropocene. The lake’s varved sediments are formed by alternating allogenic atmospheric inputs and authigenic lake processes and store a record of environmental and human impacts at a continental-global scale. Varve counting and radiometric dating provided a precise annual-resolution sediment chronology for the site. Time series records of radioactive (239,240Pu, 129I and soot 14C), chemical (spheroidal carbonaceous particles, polycyclic aromatic hydrocarbons, soot, heavy metals, δ13C, etc), physical (magnetic susceptibility and grayscale) and biological (environmental DNA) indicators all show rapid changes in the mid-20th century, coincident with clear lithological changes of the sediments. Statistical analyses of these proxies show a tipping point in 1954 CE. 239,240Pu activities follow a typical unimodal globally-distributed profile, and are proposed as the primary marker for the Anthropocene. A rapid increase in 239,240Pu activities at 88 mm depth in core SHLW21-Fr-13 (1953 CE) is synchronous with rapid changes of other anthropogenic proxies and the Great Acceleration, marking the onset of the Anthropocene. The results indicate that Sihailongwan Maar Lake is an ideal site for the Anthropocene GSSP