Abstract-Perceptual image quality assessment (IQA) aims to use computational models to measure the image quality in consistent with subjective evaluations. Visual saliency (VS) has been widely studied by psychologists, neurobiologists, and computer scientists during the last decade to investigate, which areas of an image will attract the most attention of the human visual system. Intuitively, VS is closely related to IQA in that suprathreshold distortions can largely affect VS maps of images. With this consideration, we propose a simple but very effective full reference IQA method using VS. In our proposed IQA model, the role of VS is twofold.

We recently identified ERdj3 as a component of unassembled immunoglobulin (Ig) heavy chain:BiP complexes. ERdj3 also associates with a number of other protein substrates, including unfolded light chains, a nonsecreted Ig light chain mutant, and the VSV-G ts045 mutant at the nonpermissive temperature. We produced an ERdj3 mutant that was unable to stimulate BiP's ATPase activity in vitro or to bind BiP in vivo. This mutant retained the ability to interact with unfolded protein substrates, suggesting that ERdj3 binds directly to proteins instead of via interactions with BiP. BiP remained bound to unfolded light chains longer than ERdj3, which interacted with unfolded light chains initially, but quickly disassociated before protein folding was completed. This suggests that ERdj3 may bind first to substrates and serve to inhibit protein aggregation until BiP joins the complex, whereas BiP remains bound until folding is complete. Moreover, our findings support a model where interactions with BiP help trigger the release of ERdj3 from the substrate:BiP complex.

The activity of Hsp70 proteins is regulated by accessory proteins, which include members of the DnaJ-like protein family. Characterized by the presence of a highly conserved 70-amino acid J domain, DnaJ homologues activate the ATPase activity of Hsp70 proteins and stabilize their interaction with unfolded substrates. DnaJ homologues have been identified in most organelles where they are involved in nearly all aspects of protein synthesis and folding. Within the endoplasmic reticulum (ER), DnaJ homologues have also been shown to assist in the translocation, secretion, retro-translocation, and ER-associated degradation (ERAD) of secretory pathway proteins. By using bioinformatic methods, we identified a novel mammalian DnaJ homologue, ERdj4. It is the first ER-localized type II DnaJ homologue to be reported. The signal sequence of ERdj4 remains uncleaved and serves as a membrane anchor, orienting its J domain into the ER lumen. ERdj4 colocalized with GRP94 in the ER and associated with BiP in vivo when they were co-expressed in COS-1 cells. In vitro experiments demonstrated that the J domain of ERdj4 stimulated the ATPase activity of BiP in a concentration-dependent manner. However, mutation of the hallmark tripeptide HPD (His 3 Gln) in the J domain totally abolished this activation. ERdj4 mRNA expression was detected in all human tissues examined but showed the highest level of the expression in the liver, kidney, and placenta. We found that ERdj4 was highly induced at both the mRNA and protein level in response to ER stress, indicating that this protein might be involved in either protein folding or ER-associated degradation. The endoplasmic reticulum (ER)1 is the site of synthesis and maturation of secretory pathway proteins, which include resident proteins of the endocytic and exocytic organelles as well as surface and secreted proteins. Approximately one-third of all cellular proteins are translocated into the lumen of ER, which possesses a unique oxidizing and Ca 2ϩ -rich environment, where post-translational modification, folding, and oligomerization of nascent proteins occur. ER molecular chaperones and folding enzymes associate with the newly synthesized proteins to prevent their aggregation and help them fold and assemble correctly. Through a process called ER quality control, proteins that do not mature properly are retained in the ER and are eventually targeted for ER-associated degradation (ERAD) through the action of the chaperones (1).BiP, also known as GRP78, is the mammalian ER member of the Hsp70 family and was the first component of the ER quality control apparatus to be identified (2). Hsp70 family members exist in all organisms and in all organelles, where they aid in the folding and assembly of nascent proteins and prevent their aggregation during conditions of physiological stress (3, 4). Like other Hsp70 proteins, BiP plays an essential role in the biosynthesis of proteins. In addition, BiP maintains the permeability barrier of the ER translocon during early stages of protein translocation ...

The Sec61 translocon of the endoplasmic reticulum membrane forms an aqueous pore that is gated by the lumenal Hsp70 chaperone BiP. We have explored the molecular mechanisms governing BiP-mediated gating activity, including the coupling between gating and the BiP ATPase cycle, and the involvement of the substrate-binding and J domain–binding regions of BiP. Translocon gating was assayed by measuring the collisional quenching of fluorescent probes incorporated into nascent chains of translocation intermediates engaged with microsomes containing various BiP mutants and BiP substrate. Our results indicate that BiP must assume the ADP-bound conformation to seal the translocon, and that the reopening of the pore requires an ATP binding–induced conformational change. Further, pore closure requires functional interactions between both the substrate-binding region and the J domain–binding region of BiP and membrane proteins. The mechanism by which BiP mediates translocon pore closure and opening is therefore similar to that in which Hsp70 chaperones associate with and dissociate from substrates.