Inter-domain Communication Mechanisms in an ABC Importer: A Molecular Dynamics Study of the MalFGK2E Complex

ATP-Binding Cassette transporters are ubiquitous membrane proteins that convert the energy from ATP-binding and hydrolysis into conformational changes of the transmembrane region to allow the translocation of substrates against their concentration gradient. Despite the large amount of structural and biochemical data available for this family, it is still not clear how the energy obtained from ATP hydrolysis in the ATPase domains is “transmitted” to the transmembrane domains. In this work, we focus our attention on the consequences of hydrolysis and inorganic phosphate exit in the maltose uptake system (MalFGK2E) from Escherichia coli. The prime goal is to identify and map the structural changes occurring during an ATP-hydrolytic cycle. For that, we use extensive molecular dynamics simulations to study three potential intermediate states (with 10 replicates each): an ATP-bound, an ADP plus inorganic phosphate-bound and an ADP-bound state. Our results show that the residues presenting major rearrangements are located in the A-loop, in the helical sub-domain, and in the “EAA motif” (especially in the “coupling helices” region). Additionally, in one of the simulations with ADP we were able to observe the opening of the NBD dimer accompanied by the dissociation of ADP from the ABC signature motif, but not from its corresponding P-loop motif. This work, together with several other MD studies, suggests a common communication mechanism both for importers and exporters, in which ATP-hydrolysis induces conformational changes in the helical sub-domain region, in turn transferred to the transmembrane domains via the “coupling helices”

Crystallographic Orientation Relationship with Geometrically Necessary Dislocation Accumulation During High-Temperature Deformation in RR1000 Nickel-Based Superalloy

In the current study, it is demonstrated that soft grains along 〈100〉 fiber provided a pure shear condition for easy dislocation movement leading to a relatively low dislocation density. The hard grains along the 〈111〉 fiber, however, were not favorably oriented for slip system activation and caused high dislocation accumulation. It is concluded that the average overall dislocation density does not provide a meaningful value, as it is largely dependent on the original material crystallographic texture, the numbers of hard and soft grains in the electron backscatter diffraction (EBSD) mapped area, and the grain size factor

Customer emotions in service failure and recovery encounters

Emotions play a significant role in the workplace, and considerable attention has been given to the study of employee emotions. Customers also play a central function in organizations, but much less is known about customer emotions. This chapter reviews the growing literature on customer emotions in employee–customer interfaces with a focus on service failure and recovery encounters, where emotions are heightened. It highlights emerging themes and key findings, addresses the measurement, modeling, and management of customer emotions, and identifies future research streams. Attention is given to emotional contagion, relationships between affective and cognitive processes, customer anger, customer rage, and individual differences

Treatment with clarithromycin prior to coronary artery bypass graft surgery does not prevent subsequent cardiac events

Item does not contain fulltextBACKGROUND: Recently, it has been suggested that Chlamydia pneumoniae possibly plays a possible role in the pathogenesis of atherosclerosis. We investigated whether treatment with clarithromycin prior to coronary artery bypass graft (CABG) surgery would prevent subsequent cardiovascular events and mortality. METHODS: Patients who were scheduled for CABG surgery were randomly assigned to receive either clarithromycin or placebo until the day of surgery in a double-blind trial. During the 2 years of follow-up, mortality and cardiovascular events were assessed. RESULTS: Follow-up at 2 years was achieved for 473 patients. The mean duration of treatment was 16 days. Patient characteristics at baseline were well balanced between the 2 treatment groups. Mortality was equal in the 2 groups: 10 (4.2%) of 238 patients in the clarithromycin group and 9 (3.8%) of 235 patients in the placebo group (relative risk, 1.10; 95% CI, 0.42-2.89; P=1.0). Also, there were no significant differences in the proportion of patients who experienced cardiovascular events during the follow-up period: 20 (8.4%) of 238 patients in the clarithromycin group and 19 (8.1%) of 235 patients in the placebo group (relative risk, 1.04; 95% CI, 0.55-1.98; P=1.0). The overall rate of such events was 58 (12.3%) of 473 patients. CONCLUSIONS: Treatment with clarithromycin in patients scheduled for CABG surgery did not reduce the subsequent occurrence of cardiovascular events or mortality during a 2-year follow-up period