The role of the 8-18 helix of CGRP 8-37 in mediating high affinity binding to CGRP receptors; coulombic and steric interactions

1. The role of individual residues in the 8-18 helix of CGRP 8-37 in promoting high-affinity binding to CGRP 1 receptors expressed on rat L6 and human SK-N-MC cells has been examined. The relative potencies of various derivatives were estimated from their ability to inhibit the human αCGRP-mediated increase in cyclic AMP production and the binding of [ 125I]-human αCGRP. 3. Arg 11 and Arg 18 were replaced by serines to give [Ser 11.18]CGRP 8-37. These bound with pKi values <6 to SK-N-MC cells and had apparent pA 2 values of 5.81 ± 0.04 and 5.31 ± 0.11 on SK-N-MC and L6 cells. CGRP 8-37 had a pKi of 8.22 on SK-N-MC cells and pK b values on the above cell lines of 8.95±0.04 and 8.76±0.04. 3. The arginines were replaced with glutamic acid residues. [Glu 11]CGRP 8-37 had a pK b of 7.14±0.14 on SK-N-MC cells (pKi=7.05±0.05) and 6.99±0.08 on L6 cells. [Glu 18]CGRP 8-37 had a pK b of 7.10±0.0.08 on SK-N-MC cells (pKi=6.91±0.23) and 7.12±0.09 on L6 cells. 4. Leu 12, Leu 15 and Leu 16 were replaced by benzoyl-phenylalanine (bpa) residues. On SK-N-MC cells, the apparent pA 2 values of [bpa 12]-, [bpa 15]- and [bpa 16]CGRP 8-37 were respectively 7.43±0.23, 8.34±0.11 and 5.66±0.16 (pKi values of 7.14±0.17, 7.66±0.21 and <6): on L6 cells they were 7.96±0.36, 8.28±0.21 and 6.09±0.04 (all n=3). 5. It is concluded that the Arg 11 and Arg 18 are involved in specific electrostatic interactions with other residues, either on the CGRP 1 receptors or elsewhere on CGRP 8-37. Leu 16 is in a conformationally restricted site when CGRP 8-37 binds to CGRP 1 receptors, unlike Leu 12 and Leu 15.

Workplace justice, citizenship behavior, and turnover intentions in a union context: examining the mediating role of perceived union support and union instrumentality

This study examined the relationship between workplace justice afforded by the grievance system and the union outcomes of citizenship behavior and turnover intentions and the mechanisms that underpin these relationships. Respondents (N = 187) were members of a large public sector union in Singapore. Results revealed that perceived union support and union instrumentality fully mediated the relationship between the dimensions of workplace justice and citizenship behavior directed toward the union (OCBO) and citizenship behavior directed at other union members (OCBI). Union instrumentality partially mediated the procedural justice–turnover intentions relationship.

Leader-member exchange in a Chinese context:antecedents, outcomes and mediating role of psychological empowerment

This study examines organizational antecedents of LMX and the mediating influence of empowerment on the relationships between LMX and the work outcomes of job satisfaction, task performance and psychological withdrawal behavior. Data were obtained from employees of a listed Chinese company in Guangdong Province, People's Republic of China. The results revealed that: (a) supervisor control of rewards and work unit climate were related to LMX and (b) empowerment fully mediated the relationship between LMX and the work outcomes as hypothesized.

Human resource management systems and organizational performance:a test of a mediating model in the Greek manufacturing context

This paper investigates the relationship between systems of HRM policies and organizational performance. The research is based on a sample of 178 organizations operating in the Greek manufacturing sector. A mediation model is tested to examine the link between HRM and organizational performance. The results of this study support the hypothesis that the relationship between the HRM systems of resourcing-development and reward-relations, and organizational performance, is mediated through the HRM outcomes of skills and attitudes. The paper not only supports the theory that HRM systems have a positive impact on organizational performance but also explains the mechanisms through which HRM systems improve organizational performance.

The role of commitment in foreign-Japanese relationships:mediating performance for foreign sellers in Japan

A lack of commitment between Japanese buyers and their foreign trading partners is often attributed as the cause of failure for foreign sellers in Japan. Due to Japanese idiosyncrasies, commitment plays a dominant, but poorly understood, role in the business relationship between foreign sellers and Japanese buyers. This research examines the role that the attachment bond between U.S. sellers and Japanese buyers plays in mediating the impact of exchange characteristics on performance in the domestic Japanese market. An analysis of 198 U.S. sellers in Japan demonstrates the complex web of calculative, social, and normative factors that account for the commitment existing in this foreign–Japanese trading relationship. The results highlight the importance of specific investments and cultural sensitivity for the seller’s commitment and the role of trust and switching costs in the buyer’s commitment.

The effects of external linkages on new product innovativeness:an examination of moderating and mediating influences

Our study of 116 new product development projects in Taiwanese Information Technology (IT) firms show that horizontal linkages more strongly impact on new product innovativeness than vertical linkages. The firm's learning ability or absorptive capacity increases new product innovativeness. It also moderates the impacts of corporate and research institute linkages on new product innovativeness. Moreover, we confirm that knowledge gains mediate the positive impacts of absorptive capacity and external linkages on new product innovativeness.

The role of leader-member exchanges in mediating the relationship between locus of control and work reactions

The relationship between locus of control, the quality of exchanges between subordinates and leaders (LMX), and a variety of work-related reactions (intrinsic/extrinsic job satisfaction, work-related well-being, and organizational commitment) are examined. It was predicted that people with an internal locus of control develop better quality relations with their manager and this, in turn, results in more favourable work-related reactions. Results from two different samples (N=404, and N=51) supported this prediction, and also showed that LMX either fully, or partially, mediated the relationship between locus of control and all the work-related reactions.

Central neural mechanisms mediating human visceral hypersensitivity

Although visceral hypersensitivity is thought to be important in generating symptoms in functional gastrointestinal disorders, the neural mechanisms involved are poorly understood. We recently showed that central sensitization (hyperexcitability of spinal cord sensory neurones) may play an important role. In this study, we demonstrate that after a 30-min infusion of 0.15 M HCl acid into the healthy human distal esophagus, we see a reduction in the pain threshold to electrical stimulation of the non-acid-exposed proximal esophagus (9.6 ± 2.4 mA) and a concurrent reduction in the latency of the N1 and P2 components of the esophageal evoked potentials (EEP) from this region (10.4 ± 2.3 and 15.8 ± 5.3 ms, respectively). This reduced EEP latency indicates a central increase in afferent pathway velocity and therefore suggests that hyperexcitability within the central visceral pain pathway contributes to the hypersensitivity within the proximal, non-acid-exposed esophagus (secondary hyperalgesia/allodynia). These findings provide the first electrophysiological evidence that central sensitization contributes to human visceral hypersensitivity.

Antecedents and consequences of new product development and international new product rollout timeliness:an examination of mediating and moderating influences

The study examined the relationships between antecedents, timeliness in NPD and INPR, and consequences. A conceptual framework was tested using 232 new products from South Korean firms. The hypothesized relationships among the constructs in the model were evaluated by multiple regression and hierarchal regression analyses using SPSS 12 as well as by structural equation modelling (SEM) using SIMPLIS LISREL. In addition, confirmatory factor analysis (CFA) was carried out using SIMPLIS LISREL. In the direct relationships, cross-functional linkages and marketing synergy exhibited a statistically significant effect on NPD timeliness. The results also supported the influences of the HQ-subsidiary/agent relationship and NPD timeliness on INPR timeliness as well as INPR timeliness on performance. In the mediating effect tests, marketing proficiency significantly accounts for the relationships between cross-functional linkages and NPD timeliness, between marketing synergy and NPD timeliness, and between the HQ-subsidiary/agent relationship and INPR timeliness. Technical proficiency also mediates the effect of the HQ-subsidiary/agent relationship on INPR timeliness. The influence of NPD timeliness on new product performance in target markets is attributed to INPR timeliness. As for the results of the external environmentals and standardization influences, competitive intensity moderates the relationship between NPD timeliness and new product performance. Technology change also moderates the relationship between cross-functional linkages and NPD timeliness and between timeliness in NPD and INPR and performance. Standardization has a moderating role on the relationship between NPD timeliness and INPR timeliness. This study presents the answers to research questions which concern what factors are predictors of criterion variables, how antecedents influence timeliness in NPD and INPR and when the direct relationships in the INPR process are strengthened.

A multilevel investigation of the mediating role of trust in the relationships between leadership and follower outcomes

The following research project investigated the mediating effects of individual trust in the relationships between eight leadership dimensions and follower motivation and efficacy. The research comprised of a total of three studies of which two are individual level analyses investigating the above relationship for individual followers, while the final study established the relationship between the eight dimensions and collective efficacy and group cohesion. A new measure of trust — collective vertical trust — was developed and tested and formed the mediator for the final study. The findings showed that leadership is indeed mediated through trust on both individual and collective level in the majority of relationships. In addition it was shown that individual and collective vertical trust are significantly related. Finally, the final study showed an absence of a significant relationship between trust on both the individual and collective level and organizational performance. The findings contributed to existing research in various ways: 1) the mediating effect of individual trust was established for eight separate leadership dimensions; 2) the studies established that while the indirect effects of leadership on follower motivation are similar amongst all age groups and levels of work experience, more work experienced individuals draw their beliefs in their abilities (i.e., self-efficacy) from alternative sources than leadership or trust in the leader; 3) a new measure of collective trust —collective vertical trust was established; 4) the mediating effect of collective trust was shown to be crucial in leadership effects on collective efficacy and group cohesion; and finally 5) a leadership measure initially designed for executive leaders was refined and tested for non-executive leaders.

Delegation and employee work outcome:an examination of the cultural context of mediating processes in China

We used cultural self-representation theory to develop a model of the processes linking delegation to work outcomes. We tested this model with data from a sample of 171 subordinate-supervisor dyads from the People's Republic of China. Regression results revealed that organization-based self-esteem and perceived insider status fully mediated the influence of delegation on affective organizational commitment, task performance, and innovative behavior and partially mediated delegation's influence on job satisfaction. Furthermore, traditionality moderated the relationships between delegation and the mediators in such a way that the relationships were stronger for individuals lower rather than higher in traditionality. © Academy of Management Journal.

The mediating role of discrete emotions in the relationship between injustice and counterproductive work behaviors:a study in Pakistan

Purpose: Our study explores the mediating role of discrete emotions in the relationships between employee perceptions of distributive and procedural injustice, regarding an annual salary raise, and counterproductive work behaviors (CWBs). Design/Methodology/Approach: Survey data were provided by 508 individuals from telecom and IT companies in Pakistan. Confirmatory factor analysis, structural equation modeling, and bootstrapping were used to test our hypothesized model. Findings: We found a good fit between the data and our tested model. As predicted, anger (and not sadness) was positively related to aggressive CWBs (abuse against others and production deviance) and fully mediated the relationship between perceived distributive injustice and these CWBs. Against predictions, however, neither sadness nor anger was significantly related to employee withdrawal. Implications: Our findings provide organizations with an insight into the emotional consequences of unfair HR policies, and the potential implications for CWBs. Such knowledge may help employers to develop training and counseling interventions that support the effective management of emotions at work. Our findings are particularly salient for national and multinational organizations in Pakistan. Originality/Value: This is one of the first studies to provide empirical support for the relationships between in/justice, discrete emotions and CWBs in a non-Western (Pakistani) context. Our study also provides new evidence for the differential effects of outward/inward emotions on aggressive/passive CWBs. © 2012 Springer Science+Business Media, LLC.

Leader-member exchange and contextual performance:the mediating influence of organization-based self-esteem

This study examined the mediating influence of organization-based self-esteem (OBSE) on the relationship between leader-member exchange (LMX) and contextual performance. Respondents were Indian employees and their immediate supervisors. Results of structural equation modeling (SEM) that compared the fit of a fully mediated model to a partially mediated model revealed support for the hypothesized fully mediated model. Specifically, the SEM results showed the relationship between LMX and the contextual performance facets of interpersonal facilitation and job dedication to be indirect, through OBSE. Support for the hypothesized mediating influence of OBSE highlights the multiple motivational underpinnings of contextual performance

Personality and engagement at work:the mediating role of psychological meaningfulness

In this study, we examined the associations of personality traits of the Big Five model with work engagement, and tested a theoretical model in which these associations are mediated by the positive state of psychological meaningfulness (perceptions that work is valuable and meaningful). In a sample of 238 UK working adults, we found that the personality facets assertiveness and industriousness were the strongest predictors of work engagement, and that both exhibited direct and indirect effects, mediated by psychological meaningfulness. Neuroticism demonstrated a marginal indirect association with engagement, again mediated by psychological meaningfulness. Our findings offered good support for our model, explaining a pathway from personality traits to engagement. Practical implications for management are discussed. © 2013 Wiley Periodicals, Inc.