A semi-automated mass spectrometric immunoassay coupled to selected reaction monitoring (MSIA-SRM) reveals novel relationships between circulating PCSK9 and metabolic phenotypes in patient cohorts.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of circulating low density lipoprotein cholesterol (LDL-C) levels. Besides its full-length mature form, multiple variants of PCSK9 have been reported such as forms that are truncated, mutated and/or with posttranslational modifications (PTMs). Previous studies have demonstrated that most of these variants affect PCSK9's function and thereby LDL-C levels.

USP8 regulates mitophagy by removing K6-linked ubiquitin conjugates from parkin.

Mutations in the Park2 gene, encoding the E3 ubiquitin-ligase parkin, are responsible for a familial form of Parkinson's disease (PD). Parkin-mediated ubiquitination is critical for the efficient elimination of depolarized dysfunctional mitochondria by autophagy (mitophagy). As damaged mitochondria are a major source of toxic reactive oxygen species within the cell, this pathway is believed to be highly relevant to the pathogenesis of PD.

Increased subcutaneous adipose tissue expression of genes involved in glycerolipid-fatty acid cycling in obese insulin-resistant versus -sensitive individuals.

Context: A subpopulation of obese individuals remains insulin sensitive (ISO). They represent a unique human model to investigate factors underlying insulin resistance (IR) without the confounding effect of major differences in weight/adiposity. Altered fatty-acid (FA) metabolism in sc adipose tissue (SAT) contributes to obesity-associated IR.

Rapid development of sensitive, high-throughput, quantitative and highly selective mass spectrometric targeted immunoassays for clinically important proteins in human plasma and serum.

Objectives: The aim of this study was to develop high-throughput, quantitative and highly selective mass spectrometric, targeted immunoassays for clinically important proteins in human plasma or serum.

Design And Methods: The described method coupled mass spectrometric immunoassay (MSIA), a previously developed technique for immunoenrichment on a monolithic microcolumn activated with an anti-protein antibody and fixed in a pipette tip, to selected reaction monitoring (SRM) detection and accurate quantification of targeted peptides, including clinically relevant sequence or truncated variants.

Results: In this report, we demonstrate the rapid development of MSIA-SRM assays for sixteen different target proteins spanning seven different clinically important areas (including neurological, Alzheimer's, cardiovascular, endocrine function, cancer and other diseases) and ranging in concentration from pg/mL to mg/mL.

Molecular evolution of the GapC gene family in Amsinckia spectabilis populations that differ in outcrossing rate.

Molecular evolutionary analysis of the glyceraldehyde 3-phosphate dehydrogenase (GapC) gene family was conducted in the plant genus Amsinckia (Boraginaceae), a group that exhibits marked variation in the mating system. GapC genes in this group differ from those of Arabidopsis thaliana in terms of both intron size and number. Phylogenetic and Southern hybridization analyses suggest the presence of multiple GapC loci, each defined by a set of base substitutions that are in strong linkage disequilibrium.