Summary Ca2+-Calmodulin dependent protein kinase II (CaMKII) is a regulatory node in heart and brain, and its chronic activation can be pathological. CaMKII activation seen in heart failure can directly induce pathological changes in ion channels, Ca2+ handling and gene transcription.1 Here we discover a novel mechanism linking CaMKII and hyperglycemic signaling in diabetes mellitus, which is a key risk factor for heart2 and neurodegenerative diseases.3,4 Acute hyperglycemia causes covalent modification of CaMKII by O-linked N-acetylglucosamine (O-GlcNAc). O-GlcNAc modification of CaMKII at Ser-279 activates CaMKII autonomously, creating molecular memory even after [Ca2+] declines. O-GlcNAc modified CaMKII is increased in heart and brain from diabetic humans and rats. In cardiomyocytes, increased [glucose] significantly enhances CaMKII-dependent activation of spontaneous sarcoplasmic reticulum (SR) Ca2+ release events that can contribute to cardiac mechanical dysfunction and arrhythmias.1 These effects were prevented by pharmacological inhibition of O-GlcNAc signaling or genetic ablation of CaMKIIδ. In intact perfused hearts, arrhythmias were enhanced by increased [glucose] via O-GlcNAc-and CaMKII-dependent pathways. In diabetic animals, acute blockade of O-GlcNAc inhibited arrhythmogenesis. Thus, O-GlcNAc modification of CaMKII is a novel signaling event in pathways that may contribute critically to cardiac and neuronal pathophysiology in diabetes and other diseases.

Rationale Calcium/calmodulin dependent protein kinase II (CaMKII) is a key mediator of intracellular signaling in the heart. However, the tools currently available for assessing dynamic changes in CaMKII localization and activation in living myocytes are limited. Objective Here we use Camui, a novel FRET based biosensor in which full length CaMKII is flanked by CFP and YFP, to measure CaMKII activation state in living rabbit myocytes. Methods and Results We show that Camui and mutant variants which lack the sites of CaMKII autophosphorylation (T286A) and oxidative regulation (CM280/1VV) serve as useful biosensors for CaMKIIδ activation state. Camui (WT or mutant) was expressed in isolated adult cardiac myocytes and localization and CaMKII activation state were determined using confocal microscopy. Camui, like CaMKIIδ is concentrated at the z-lines, with low baseline activation state. Camui activation increased directly with pacing frequency, but the maximal effect was blunted with the T286A, consistent with frequency dependent phosphorylation of CaMKII at T286 mainly at high frequency and amplitude Ca transients. Camui was also activated by four neurohormonal agonists. Angiotensin II and endothelin-1 activated Camui, largely via an oxidation-dependent mechanism, while isoproterenol and phenylephrine mediated mechanisms had a significant autophosphorylation-dependent component. Conclusions Camui is a novel, non-destructive tool that allows spatio-temporally resolved measurement of CaMKII activation state in physiologically functioning myocytes. This represents a first step in using Camui to elucidate key mechanistic details of CaMKII signaling in live hearts and myocytes.

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This paper examines the phenomenon of trust spirals in small groups. Drawing on literature on the spiral reinforcement of trust, we theorize that diversity in propensity to trust has affective and cognitive consequences related to trust (i.e., feelings of frustration and perceptions of low similarity), reducing the level of experienced intragroup trust early in a group's development. Reduced experienced trust then fuels relationship conflict and lowers trust even further over time, ultimately having a negative effect on group performance. These ideas are tested using a sample of MBA student groups surveyed at 3 time periods over 4 months. Results confirm our hypothesis that diversity in propensity to trust is sufficient to trigger a downward trust spiral and poor performance in small groups.

The study results indicate that comprehensive school food policies can favourably influence the foods and drinks provided on school premises and can be highly acceptable to key stakeholders, without adversely affecting profitability. The results are encouraging for policy makers in other jurisdictions considering the implementation of similar policies.

Teams scholars have historically conceptualized and measured intragroup conflict at the team level. But emerging evidence suggests that perceptions of intragroup conflict are often not uniform, shared, or static. These findings suggest important questions about the microfoundations of intragroup conflict: Where does conflict within teams originate? And how does it evolve over time? We address these and other questions in three abductive studies. We consider four origination points—an individual, dyad, subgroup, or team—and three evolutionary trajectories—conflict continuity, contagion, and concentration. Study 1, a qualitative study of narrative accounts, and Study 2, a longitudinal social networks study of student teams, reveal that fewer than 30 percent of teams experience team-level conflict. Instead, conflict more commonly originates and persists at individual, dyadic, or subgroup levels. Study 2 further demonstrates that traditional psychometric intragroup conflict scales mask the existence of these various origins and trajectories of conflict. Study 3, a field study of manufacturing teams, reveals that individual and dyadic task conflict origins positively predict team performance, whereas traditional intragroup task conflict measures negatively predict team performance. The results raise serious concerns about current methods and theory in the team conflict literature and suggest that researchers must go beyond team-level conceptualizations of conflict.

We examine how "top management team (TMT) misfit," or discrepancies between the TMT's functional roles and the qualifications of the managers who fill those roles, affects the evolution of TMT composition and structure in a longitudinal study of entrepreneurial ventures. We distinguish two types of misfit-overqualification and underqualificationand study how each is associated with TMT changes. We further consider the moderating effect of firm development. Results reveal that underqualified TMTs hire new managers to reinforce existing capabilities whereas overqualified TMTs elaborate their role structures. However, achieving developmental milestones (i.e., obtaining venture capital funding and staging an initial public offering) is a critical contingency to TMT change: absent these milestones, firms neither hire new managers nor add roles, even when they seemingly need to do so. These findings contribute to knowledge of how TMTs and new ventures evolve by underscoring the importance of simultaneously attending to TMT composition and structure.

ObjectiveThe Healthy Food and Drink Policy was implemented in Western Australian government schools in 2007. The aim of the present study was to assess the compliance of Western Australian school canteen menus with the policy a decade after its introduction.DesignThe traffic-light system that underpins the Healthy Food and Drink Policy categorises foods and drinks into three groups: ‘green’ healthy items, ‘amber’ items that should be selected carefully and ‘red’ items that lack nutritional value. Canteen menus were collected online and each menu item was coded as a green, amber or red choice.SettingWestern Australia.ParticipantsOnline canteen menus from 136 primary and secondary government schools.ResultsThe majority of audited school menus met policy requirements to include ≥60 % green items (84 %) and ≤40 % amber items (90 %), but only 52 % completely excluded red items. Overall, approximately half (48 %) of school canteen menus met all three traffic-light targets. On average, 70 % of the menu items were green, 28 % were amber and 2 % were red. Primary-school canteen menus were more likely than those from secondary schools to meet the requirements of the policy.ConclusionsWhile the sampled Western Australian government school canteen menus were highly compliant with most of the requirements of the Healthy Food and Drink Policy, many offered red foods and/or drinks. Providing all schools with further education about identifying red items and offering additional services to secondary schools may help improve compliance rates.