Glycine311, a determinant of paxilline block in BK channels: a novel bend in the BK S6 helix

The tremorogenic fungal metabolite, paxilline, is widely used as a potent and relatively specific blocker of Ca2+- and voltage-activated Slo1 (or BK) K+ channels. The pH-regulated Slo3 K+ channel, a Slo1 homologue, is resistant to blockade by paxilline. Taking advantage of the marked differences in paxilline sensitivity and the homology between subunits, we have examined the paxilline sensitivity of a set of chimeric Slo1/Slo3 subunits. Paxilline sensitivity is associated with elements of the S5–P loop–S6 module of the Slo1 channel. Replacement of the Slo1 S5 segment or the second half of the P loop results in modest changes in paxilline sensitivity. Replacing the Slo1 S6 segment with the Slo3 sequence abolishes paxilline sensitivity. An increase in paxilline affinity and changes in block kinetics also result from replacing the first part of the Slo1 P loop, the so-called turret, with Slo3 sequence. The Slo1 and Slo3 S6 segments differ at 10 residues. Slo1-G311S was found to markedly reduce paxilline block. In constructs with a Slo3 S6 segment, S300G restored paxilline block, but most effectively when paired with a Slo1 P loop. Other S6 residues differing between Slo1 and Slo3 had little influence on paxilline block. The involvement of Slo1 G311 in paxilline sensitivity suggests that paxilline may occupy a position within the central cavity or access its blocking position through the central cavity. To explain the differences in paxilline sensitivity between Slo1 and Slo3, we propose that the G311/S300 position in Slo1 and Slo3 underlies a structural difference between subunits in the bend of S6, which influences the occupancy by paxilline

Communication Predicts Medication Self-Efficacy in Glaucoma Patients

Medication self-efficacy, or patients’ confidence that they can perform medication-related behaviors, is associated with better glaucoma medication adherence. Little is known about how to enhance glaucoma patients’ medication self-efficacy. Our purpose is to examine whether patient-provider communication increases glaucoma patients’ medication self-efficacy

The structure of a class 3 nonsymbiotic plant haemoglobin from<i>Arabidopsis thaliana</i>reveals a novel N-terminal helical extension

Plant nonsymbiotic haemoglobins fall into three classes, each with distinct properties but all with largely unresolved physiological functions. Here, the first crystal structure of a class 3 nonsymbiotic plant haemoglobin, that fromArabidopsis thaliana, is reported to 1.77 Å resolution. The protein forms a homodimer, with each monomer containing a two-over-two α-helical domain similar to that observed in bacterial truncated haemoglobins. A novel N-terminal extension comprising two α-helices plays a major role in the dimer interface, which occupies the periphery of the dimer–dimer face, surrounding an open central cavity. The haem pocket contains a proximal histidine ligand and an open sixth iron-coordination site with potential for a ligand, in this structure hydroxide, to form hydrogen bonds to a tyrosine or a tryptophan residue. The haem pocket appears to be unusually open to the external environment, with another cavity spanning the entrance of the two haem pockets. The final 23 residues of the C-terminal domain are disordered in the structure; however, these domains in the functional dimer are adjacent and include the only two cysteine residues in the protein sequence. It is likely that these residues form disulfide bondsin vitroand it is conceivable that this C-terminal region may act in a putative complex with a partner moleculein vivo.</jats:p

Accuracy of Patient-reported Adherence to Glaucoma Medications on a Visual Analog Scale Compared With Electronic Monitors

Glaucoma medications can reduce intraocular pressure and improve clinical outcomes when patients adhere to their medication regimen. Providers often ask glaucoma patients to self-report their adherence, but the accuracy of this self-report method has received little scientific attention. Our purpose was to compare a self-report medication adherence measure with adherence data collected from Medication Event Monitoring Systems (MEMS) electronic monitors. Additionally, we sought to identify which patient characteristics were associated with over-reporting adherence on the self-reported measure

Exploring the influence of patient-provider communication on intraocular pressure in glaucoma patients

We examined whether six patient-provider communication behaviors directly affected the intraocular pressure (IOP) of glaucoma patients or whether patient medication adherence and eye drop technique mediated the relationship between self-efficacy, communication, and IOP

Applying the resources and supports in self-management framework to examine ophthalmologist-patient communication and glaucoma medication adherence

Little is known about how ophthalmologist-patient communication over time is associated with glaucoma patient long-term adherence. The purpose of our study was to examine the association between provider use of components of the resources and supports in self-management model when communicating with patients and adherence to glaucoma medications measured electronically over an 8-month period. In this longitudinal prospective cohort study, the main variables studied were ophthalmologist communication-individualized assessment, collaborative goal setting and skills enhancement. Patients with glaucoma who were newly prescribed or on glaucoma medications were recruited from six ophthalmology clinics. Patients’ baseline and next follow-up visits were videotape-recorded. Patients were interviewed after their visits. Patients used medication event monitoring systems (MEMS) for 8 months after enrollment into the study, and adherence was measured electronically using MEMS for 240 days after their visits. Two hundred and seventy-nine patients participated. Patient race and regimen complexity were negatively associated with glaucoma medication adherence over an 8-month period. Provider communication behaviors, including providing education and positive reinforcement, can improve patient adherence to glaucoma medications over an 8-month period

Global food security and food riots – an agent-based modelling approach

Due to negative consequences of climate change for agriculture and food production shocks affecting different areas of the world, the past two decades saw the conditions of global food security increasingly worsen. This has resulted in negative consequences for the world economy, partly causing international food price spikes and social upheavals. In this paper we present statistical findings along with a preliminary version of an original agent-based model called the Dawe Global Security Model that simulates the global food market and the political fragility of countries. The model simulates the effects of food insecurity on international food prices and how these, coupled with national political fragility and international food trade can, in turn, increase the probability of food riots in countries. The agents in the model are the 213 countries of the world whose characteristics reflect empirical data and the international trade of food is also simulated based on real trade partnerships and data. The model has been informed, calibrated and validated using real data and the results of these procedures are presented in the paper. To further test the model we also present the model’s forecasts for the near future in terms of food prices and incidence of food riots. The Dawe Global Security Model can be used to test scenarios on the evolution of shocks to global food production and analyse consequences for food riots. Further developments of the model can include national responses to food crises to investigate how countries can influence the spread of global food crises

Ophthalmologist–Patient Communication, Self-efficacy, and Glaucoma Medication Adherence

The objective of the study was to examine the association between provider-patient communication, glaucoma medication adherence self-efficacy, outcome expectations, and glaucoma medication adherence