Side chain oxygenated cholesterol regulates cellular cholesterol homeostasis through direct sterol-membrane interactions.

Side chain oxysterols exert cholesterol homeostatic effects by suppression of sterol regulatory element-binding protein maturation and promoting degradation of hydroxymethylglutaryl-CoA reductase. To examine whether oxysterol-membrane interactions contribute to the regulation of cellular cholesterol homeostasis, we synthesized the enantiomer of 25-hydroxycholesterol. Using this unique oxysterol probe, we provide evidence that oxysterol regulation of cholesterol homeostatic responses is not mediated by enantiospecific oxysterol-protein interactions. We show that side chain oxysterols, but not steroid ring-modified oxysterols, exhibit membrane expansion behavior in phospholipid monolayers and bilayers in vitro. This behavior is non-enantiospecific and is abrogated by increasing the saturation of phospholipid acyl chain constituents. Moreover, we extend these findings into cultured cells by showing that exposure to saturated fatty acids at concentrations that lead to endoplasmic reticulum membrane phospholipid remodeling inhibits oxysterol activity. These studies implicate oxysterol-membrane interactions in acute regulation of sterol homeostatic responses and provide new insights into the mechanism through which oxysterols regulate cellular cholesterol balance.

Knowledge and skills that facilitate the personal support dimension of citizenship.

Efforts to identify the individual attributes that predict organizational citizenship have focused largely on dispositional factors. This focus reflects an unstated assumption that anyone can engage in successful citizenship, but only some choose to do so. The authors contend that, although this may be true of some dimensions of citizenship, it is not true of others. Based on a review of research from industrial and organizational psychology, management, education, clinical psychology, conflict resolution, and other literatures, the authors offer a set of 15 propositions linking knowledge and skill variables to the 4 personal support dimensions of citizenship performance.

Conscientiousness and reactions to psychological contract breach: a longitudinal field study.

The authors examined the role of employee conscientiousness as a moderator of the relationships between psychological contract breach and employee behavioral and attitudinal reactions to the breach. They collected data from 106 newly hired employees within the 1st month of employment (Time 1), 3 months later (Time 2), and 8 months after Time 1 (Time 3) to observe the progression through contract development, breach, and reaction. Results suggest that conscientiousness is a significant moderator for 4 of the 5 contract breach-employee reaction relationships examined (turnover intentions, organizational loyalty, job satisfaction, and 1 of 2 facets of job performance). Specifically, employees who were lower in conscientiousness had more negative reactions to perceived breach with respect to turnover intentions, organizational loyalty, and job satisfaction. In contrast, employees who were higher in conscientiousness reduced their job performance to a greater degree in response to contract breach. Future research directions are discussed.

A meta-analytic investigation of conscientiousness in the prediction of job performance: examining the intercorrelations and the incremental validity of narrow traits.

Researchers of broad and narrow traits have debated whether narrow traits are important to consider in the prediction of job performance. Because personality-performance relationship meta-analyses have focused almost exclusively on the Big Five, the predictive power of narrow traits has not been adequately examined. In this study, the authors address this question by meta-analytically examining the degree to which the narrow traits of conscientiousness predict above and beyond global conscientiousness. Results suggest that narrow traits do incrementally predict performance above and beyond global conscientiousness, yet the degree to which they contribute depends on the particular performance criterion and occupation in question. Overall, the results of this study suggest that there are benefits to considering the narrow traits of conscientiousness in the prediction of performance.

Racial differences in socially desirable responding in selection contexts: magnitude and consequences.

Two studies were conducted to examine the magnitude and consequences of racial differences on social desirability (SD) scales. Study 1 included 1,063 job applicants, and Study 2 included 3 sets of incumbents (total N = 534). In both studies, participants were administered several personality measures and an SD scale. Across all samples, Whites scored lower on the SD scale than Blacks (average d = .37), Hispanics (average d = .47), and Asians (average d = 1.04), but these differences were not observed on the personality scales. The consequence of differences in socially desirable responding (SDR) is that fewer minority group members would be selected if SD scales were used to derive cut scores to eliminate individuals from the applicant pool or if the scales were used to correct personality test scores for SDR. However, applying the SD correction did not affect the validity of the personality test for any of the racial groups. Overall, our findings suggest that researchers and practitioners should consider the use of SD scales very carefully, as their use may have unintended consequences. These studies also demonstrate a need to closely examine the construct validity of SD measures across diverse groups.

The sterol-sensing domain of the Niemann-Pick C1 (NPC1) protein regulates trafficking of low density lipoprotein cholesterol.

The Niemann-Pick C1 (NPC1) protein is a key participant in intracellular sterol trafficking and regulation of cholesterol homeostasis. NPC1 contains a pentahelical region that is evolutionarily related to sterol-sensing domains found in other polytopic proteins involved in sterol interactions or sterol metabolism, including sterol regulatory element-binding protein cleavage-activating protein and hydroxymethylglutaryl-CoA reductase. To gain insight into the role of the sterol-sensing domain of NPC1, we examined the effect of point mutations in the NPC1 sterol-sensing domain on the trafficking of low density lipoprotein-derived cholesterol and sphingolipids. We show that an NPC1 P692S loss of function mutation results in decreased cholesterol delivery to the plasma membrane and endoplasmic reticulum. By contrast, NPC1 proteins carrying a L657F or D787N point mutation, which correspond to the activating SCAP L315F and D443N mutations, respectively, exhibit a gain of function phenotype. Specifically, cell lines expressing the NPC1 L657F or D787N mutations show a nearly 2-fold increase in the rates of low density lipoprotein cholesterol trafficking to the plasma membrane and to the endoplasmic reticulum, and more rapid suppression of sterol regulatory element-binding protein-dependent gene expression. Trafficking of sphingolipids is intact in the D787N and L657F cell lines. Our finding that D787N and L657F are activating NPC1 mutations provide evidence for a conserved mechanism for the sterol-sensing domain among cholesterol homeostatic proteins.