Background:The functional importance of apolipoprotein A-I (apoA-I) nitration at tyrosine 166 (Tyr 166 ) in vivo is controversial. Results: Nitrotyrosine 166-apoA-I accounts for 8% of apoA-I within human atheroma, is not HDL-associated, and is functionally impaired. Conclusion: Buoyant density ultracentrifugation of HDL can lead to erroneous results, particularly with modified apoA-I forms. Significance: Detection and quantification of nitrotyrosine 166-apoA-I may provide insights into a pathophysiological process within the artery wall.

Cholesterol from peripheral tissues, such as within the artery wall, is transported to the liver by high density lipoprotein (HDL) particles, which are continuously remodeled in a process called reverse cholesterol transport ( 1, 2 ). HDL particles are highly heterogeneous, varying in protein and lipid content ( 3 ). Apolipoprotein A1 (apoA1) is Abstract Small-angle neutron scattering (SANS) with contrast variation was used to obtain the low-resolution structure of nascent HDL (nHDL) reconstituted with dimyristoyl phosphatidylcholine (DMPC) in the absence and presence of cholesterol, [apoA1:DMPC (1:80, mol:mol) and apoA1:DMPC:cholesterol (1:86:9, mol:mol:mol)]. The overall shape of both particles is discoidal with the low-resolution structure of apoA1 visualized as an open, contorted, and out of plane conformation with three arms in nascent HDL/dimyristoyl phosphatidylcholine without cholesterol (nHDL DMPC ) and two arms in nascent HDL/dimyristoyl phosphatidylcholine with cholesterol (nHDL DMPC+Chol ). The low-resolution shape of the lipid phase in both nHDL DMPC and nHDL DMPC+Chol were oblate ellipsoids, and fi t well within their respective protein shapes. Modeling studies indicate that apoA1 is folded onto itself in nHDL DMPC , making a large hairpin, which was also confi rmed independently by both cross-linking mass spectrometry and hydrogen-deuterium exchange (HDX) mass spectrometry analyses. In nHDL DMPC+Chol , the lipid was expanded and no hairpin was visible. Importantly, despite the overall discoidal shape of the whole particle in both nHDL DMPC Press, January 23, 2013 DOI 10.1194 The low-resolution structure of nHDL reconstituted with DMPC with and without cholesterol reveals a mechanism for particle expansion Abbreviations: DMPC, dimyristoyl phosphatidylcholine; DSH, double super helix; ESR, electron spin resonance; FRET, fl uorescence resonance energy transfer; HDX, hydrogen-deuterium exchange; LUV, large unilamellar vesicle; nHDL, nascent HDL; nHDL DMPC , nascent HDL/dimyristoyl phosphatidylcholine without cholesterol; nHDL DMPC+Chol , nascent HDL/dimyristoyl phosphatidylcholine with cholesterol; nHDL POPC , nascent HDL/POPC and cholesterol; PC, phosphatidyl choline ; POPC, 1-palmitoyl-2-oleoyl-sn -glycero-3-phosphocholine; q , range of momentum transfer; SANS, small-angle neutron scattering; SCX, strong-cation exchange. Published, JLR Papers in

The goal of endodontic treatment is to remove all the vital and necrotic tissues, microorganisms and microbial byproducts from root canal system. This goal can be achieved through chemical and mechanical debridement of root canals. This article narrates the specifics and requirements of the irrigation solutions. Sodium hypochlorite is proposed as the primary irrigant by virtue of its organic tissue dissolution capacity and broad antimicrobial properties. On the other hand, chelation solutions are recommended as auxiliary solutions to remove the smear layer or to hinder its formation on dentin surface. Thus, it's hoped that sealers and root canal fillers can penetrate to dentin tubules and obturate the canals hermetically. There are new studies on traditional irrigants especially on some irrigants that can replace sodium hypoclorite. This article reviews the new irrigants which can be used in future endodontic practice, and their advantages and limitations. Moreover, actions and interactions of recently used irrigants are adverted.

Aminoacyl-tRNA synthetases are ubiquitous, evolutionarily conserved enzymes catalyzing the conjugation of amino acids onto cognate tRNAs. During eukaryotic evolution, tRNA synthetases have been the targets of persistent structural modifications. These modifications can be additive, as in the evolutionary acquisition of noncatalytic domains, or subtractive, as in the generation of truncated variants through regulated mechanisms such as proteolytic processing, alternative splicing, or coding region polyadenylation. A unique variant is the human glutamyl-prolyl-tRNA synthetase (EPRS) consisting of two fused synthetases joined by a linker containing three copies of the WHEP domain (termed by its presence in tryptophanyl-, histidyl-, and glutamyl-prolyl-tRNA synthetases). Here, we identify site-selective proteolysis as a mechanism that severs the linkage between the EPRS synthetases and Caspase action targeted Asp-929 in the third WHEP domain, thereby separating the two synthetases. Using a neoepitope antibody directed against the newly exposed C terminus, we demonstrate EPRS cleavage at Asp-929 and Biochemical and biophysical characterizations of the N-terminally generated EPRS proteoform containing the glutamyl-tRNA synthetase and most of the linker, including two WHEP domains, combined with structural analysis by small-angle neutron scattering, revealed a role for the WHEP domains in modulating conformations of the catalytic core and GSH--transferase-C-terminal-like (GST-C) domain. WHEP-driven conformational rearrangement altered GST-C domain interactions and conferred distinct oligomeric states in solution. Collectively, our results reveal long-range conformational changes imposed by the WHEP domains and illustrate how noncatalytic domains can modulate the global structure of tRNA synthetases in complex eukaryotic systems.