Search

Protein remote homology detection is one of the most fundamental research tool for protein structure and function prediction. Most search methods for protein remote homology detection are evaluated based on the Structural Classification of Proteins-extended (SCOPe) benchmark, but the diverse hierarchical structure relationships between the query protein and candidate proteins are ignored by these methods. In order to further improve the predictive performance for protein remote homology detection, a search framework based on the predicted protein hierarchical relationships (PHR-search) is proposed. In the PHR-search framework, the superfamily level prediction information is obtained by extracting the local and global features of the Hidden Markov Model (HMM) profile through a convolution neural network and it is converted to the fold level and class level prediction information according to the hierarchical relationships of SCOPe. Based on these predicted protein hierarchical relationships, filtering strategy and re-ranking strategy are used to construct the two-level search of PHR-search. Experimental results show that the PHR-search framework achieves the state-of-the-art performance by employing five basic search methods, including HHblits, JackHMMER, PSI-BLAST, DELTA-BLAST and PSI-BLASTexB. Furthermore, the web server of PHR-search is established, which can be accessed at http://bliulab.net/PHR-search. [ABSTRACT FROM AUTHOR]

Aims Jumonji domain-containing protein 3 (JMJD3), also called lysine specific demethylase 6B (KDM6b), is an inducible histone demethylase which plays an important role in many biological processes, however, its function in vascular remodelling remains unknown. We aim to demonstrate that JMJD3 mediates vascular neointimal hyperplasia following carotid injury, and proliferation and migration in platelet-derived growth factor BB (PDGF-BB)-induced vascular smooth muscle cells (VSMCs). Methods and results By using both genetic and pharmacological approaches, our study provides the first evidence that JMJD3 controls PDGF-BB-induced VSMCs proliferation and migration. Furthermore, our in vivo mouse and rat intimal thickening models demonstrate that JMJD3 is a novel mediator of neointima formation based on its mediatory effects on VSMCs proliferation, migration, and phenotypic switching. We further show that JMJD3 ablation by small interfering RNA or inhibitor GSK J4 can suppress the expression of NADPH oxidase 4 (Nox4), which is correlated with H3K27me3 enrichment around the gene promoters. Besides, deficiency of JMJD3 and Nox4 prohibits autophagic activation, and subsequently attenuates neointima and vascular remodelling following carotid injury. Above all, the increased expression of JMJD3 and Nox4 is further confirmed in human atherosclerotic arteries plaque specimens. Conclusions JMJD3 is a novel factor involved in vascular remodelling. Deficiency of JMJD3 reduces neointima formation after vascular injury by a mechanism that inhibits Nox4-autophagy signalling activation, and suggesting JMJD3 may serve as a perspective target for the prevention and treatment of vascular diseases. [ABSTRACT FROM AUTHOR]