Conditions that Stabilize Membrane Domains Also Antagonize n-Alcohol Anesthesia

Diverse molecules induce general anesthesia with potency strongly correlated with both their hydrophobicity and their effects on certain ion channels. We recently observed that several n -alcohol anesthetics inhibit heterogeneity in plasma-membrane-derived vesicles by lowering the critical temperature (Tc) for phase separation. Here, we exploit conditions that stabilize membrane heterogeneity to further test the correlation between the anesthetic potency of n -alcohols and effects on Tc. First, we show that hexadecanol acts oppositely to n -alcohol anesthetics on membrane mixing and antagonizes ethanol-induced anesthesia in a tadpole behavioral assay. Second, we show that two previously described “intoxication reversers” raise Tc and counter ethanol’s effects in vesicles, mimicking the findings of previous electrophysiological and behavioral measurements. Third, we find that elevated hydrostatic pressure, long known to reverse anesthesia, also raises Tc in vesicles with a magnitude that counters the effect of butanol at relevant concentrations and pressures. Taken together, these results demonstrate that ΔTc predicts anesthetic potency for n-alcohols better than hydrophobicity in a range of contexts, supporting a mechanistic role for membrane heterogeneity in general anesthesia

Secondary structure encodes a cooperative tertiary folding funnel in the Azoarcus ribozyme

A requirement for specific RNA folding is that the free-energy landscape discriminate against non-native folds. While tertiary interactions are critical for stabilizing the native fold, they are relatively non-specific, suggesting additional mechanisms contribute to tertiary folding specificity. In this study, we use coarse-grained molecular dynamics simulations to explore how secondary structure shapes the tertiary free-energy landscape of the Azoarcus ribozyme. We show that steric and connectivity constraints posed by secondary structure strongly limit the accessible conformational space of the ribozyme, and that these so-called topological constraints in turn pose strong free-energy penalties on forming different tertiary contacts. Notably, native A-minor and base-triple interactions form with low conformational free energy, while non-native tetraloop/tetraloop–receptor interactions are penalized by high conformational free energies. Topological constraints also give rise to strong cooperativity between distal tertiary interactions, quantitatively matching prior experimental measurements. The specificity of the folding landscape is further enhanced as tertiary contacts place additional constraints on the conformational space, progressively funneling the molecule to the native state. These results indicate that secondary structure assists the ribozyme in navigating the otherwise rugged tertiary folding landscape, and further emphasize topological constraints as a key force in RNA folding

Do nursing and pharmacy students practice what they preach on safe drug storage and disposal? A cross-sectional study

Background: Research has confirmed a lack of knowledge regarding the risks of unused medications including diversion, misuse, or accidental overdose among health care professionals (Abdulmajeed, 2020). Nurses and pharmacists are often who patients interact with the most regarding medications; therefore, early education on proper storage and disposal is vital (Bowen, Rotz, Patterson, & Sen, 2017; Celio, Ninane, Bugnon, & Schneider, 2018). Objectives: The study\u27s objective is to explore safe drug storage and disposal knowledge, attitudes, and practices of professional pharmacy (Pharm.D.) and nursing students. Design: This research is an exploratory cross-sectional study from May to September 2019. Methods: An anonymous online survey was administered to a purposive sample of Pharm.D. and nursing students who were 18 years and older and enrolled in the site\u27s accredited Pharm.D. and nursing programs (N = 210). Responses were analyzed using descriptive statistics. Results: Common disposal methods reported by students of their personal medications such as pills and liquids included discarding medications with the household trash (range 30% to 55%) and medication disposal products/bag (range 19% to 28%). More than half of the participants (50.4%) had unused prescription medication at home, 35% kept the medication for later use, and almost 20% of the participants reported sharing personal medications with others. Conclusion: Although the majority of student participants had adequate knowledge of the appropriate methods for safe drug disposal, few reported using them for their own personal medications. The findings suggest there is a disconnect between the participants\u27 knowledge of the appropriate methods of safe drug storage and disposal in a professional setting and their own practices. Further research is needed to explore and address the reasons for this disconnect. Additionally, findings from this research will assist in the development of and/or the improvement of interdisciplinary educational materials among pharmacy and nursing students

The Impact of Conservation on the Status of the World\u27s Vertebrates

Using data for 25,780 species categorized on the International Union for Conservation of Nature Red List, we present an assessment of the status of the world\u27s vertebrates. One-fifth of species are classified as Threatened, and we show that this figure is increasing: On average, 52 species of mammals, birds, and amphibians move one category closer to extinction each year. However, this overall pattern conceals the impact of conservation successes, and we show that the rate of deterioration would have been at least one-fifth again as much in the absence of these. Nonetheless, current conservation efforts remain insufficient to offset the main drivers of biodiversity loss in these groups: agricultural expansion, logging, overexploitation, and invasive alien species

The Vehicle, April 1959, Vol. 1 no. 1

Vol. 1, No. 1 Table of Contents Aunt OraHelen Leepage 3 Ethnocentrismpage 7 FashionsLinda Lyonspage 7 On Giving Up Auden in DespairHelen Leepage 8 The Vagaries of ComplianceHelen Leepage 8 The StormJean Nightingalepage 9 Sonnet to SubjectWayne Nelmspage 9 The Killing of Mr. KitAl Brookspage 10 ShortsC.E.S.page 16https://thekeep.eiu.edu/vehicle/1000/thumbnail.jp

Test-retest reliability of capability measurement in the UK general population

Although philosophically attractive, it may be difficult, in practice, to measure individuals' capabilities (what they are able to do in their lives) as opposed to their functionings (what they actually do). To examine whether capability information could be reliably self-reported, we administered a measure of self-reported capability (the Investigating Choice Experiments Capability Measure for Adults, ICECAP-A) on two occasions, 2 weeks apart, alongside a self-reported health measure (the EuroQol Five Dimensional Questionnaire with 3 levels, EQ-5D-3L). We found that respondents were able to report capabilities with a moderate level of consistency, although somewhat less reliably than their health status. The more socially orientated nature of some of the capability questions may account for the difference. © 2014 The Authors Health Economics Published by John Wiley & Sons Ltd

Assistive Technology and Performance Behaviours in Music Improvisation.

The findings from three trial workshops with a group of music-learners with physical disabilities have culminated in an initial design for a novel interactive music-generation system. Using a variety of commercially available music-technologies in a synchronised set-up, the target group identified those aspects of both music production and accessible interaction that were most appealing and productive. The proposed design places equal emphasis on improvisation and accessibility, generating rhythmic, harmonic and melodic patterns that an individual can trigger and manipulate. The system will also allow a group of improvisers to work together offering variable levels of synchronization based on individual need or preference. A prototype system is currently under development