ABC transporter architecture and mechanism: implications from the crystal structures of BtuCD and BtuF

AbstractABC transporters are ubiquitous membrane proteins that facilitate unidirectional substrate translocation across the lipid bilayer. Over the past five years, new crystal structures have advanced our understanding of how ABC transporters couple adenosine triphosphate (ATP) hydrolysis to substrate transport. In the following, we will briefly review the results of these structural investigations and outline their mechanistic implications

Willow Creek, California Tourism Analysis

The primary objective of this study was to introduce and recommend different strategies for the city of Willow Creek, California to increase tourism post-Covid-19. After extensive research, the report outlines various opportunities that the Recreation 365 class, Tourism Industry Management, believe will help Willow Creek in their efforts to attract their target audience

Examining the reproducibility of meta-analyses in psychology:A preliminary report

Meta-analyses are an important tool to evaluate the literature. It is essential that meta-analyses can easily be reproduced to allow researchers to evaluate the impact of subjective choices on meta-analytic effect sizes, but also to update meta-analyses as new data comes in, or as novel statistical techniques (for example to correct for publication bias) are developed. Research in medicine has revealed meta-analyses often cannot be reproduced. In this project, we examined the reproducibility of meta-analyses in psychology by reproducing twenty published meta-analyses. Reproducing published meta-analyses was surprisingly difficult. 96% of meta-analyses published in 2013-2014 did not adhere to reporting guidelines. A third of these meta-analyses did not contain a table specifying all individual effect sizes. Five of the 20 randomly selected meta-analyses we attempted to reproduce could not be reproduced at all due to lack of access to raw data, no details about the effect sizes extracted from each study, or a lack of information about how effect sizes were coded. In the remaining meta-analyses, differences between the reported and reproduced effect size or sample size were common. We discuss a range of possible improvements, such as more clearly indicating which data were used to calculate an effect size, specifying all individual effect sizes, adding detailed information about equations that are used, and how multiple effect size estimates from the same study are combined, but also sharing raw data retrieved from original authors, or unpublished research reports. This project clearly illustrates there is a lot of room for improvement when it comes to the transparency and reproducibility of published meta-analyses

The Pneumococcal Iron Uptake Protein a (PiuA) Specifically Recognizes Tetradentate FeIIIbis- and Mono-Catechol Complexes

Streptococcus pneumoniae (Spn) is an important Gram-positive human pathogen that causes millions of infections worldwide with an increasing occurrence of antibiotic resistance. Fe acquisition is a crucial virulence determinant in Spn; further, Spn relies on exogenous FeIII-siderophore scavenging to meet nutritional Fe needs. Recent studies suggest that the human catecholamine stress hormone, norepinephrine (NE), facilitates Fe acquisition in Spn under conditions of transferrin-mediated Fe starvation. Here we show that the solute binding lipoprotein PiuA from the piu Fe acquisition ABC transporter PiuBCDA, previously described as an Fe-hemin binding protein, binds tetradentate catechol FeIII complexes, including NE and the hydrolysis products of enterobactin. Two protein-derived ligands (H238, Y300) create a coordinately-saturated FeIII complex, which parallel recent studies in the Gram-negative intestinal pathogen Campylobacter jejuni. Our in vitro studies using NMR spectroscopy and 54Fe LC-ICP-MS confirm the FeIII can move from transferrin to apo-PiuA in a NE-dependent manner. Structural analysis of PiuA FeIII-bis-catechol and GaIII-bis-catechol and GaIII-(NE)2 complexes by NMR spectroscopy reveals only localized structural perturbations in PiuA upon ligand binding, largely consistent with recent descriptions of other solute binding proteins of type II ABC transporters. We speculate that tetradentate FeIII complexes formed by mono- and bis-catechol species are important Fe sources in Gram-positive human pathogens, since PiuA functions in the same way as SstD from Staphylococcus aureus

The Impact of Surface Cleaning Restoration of Paintings On Observers\u27 Eye Fixation Patterns and Artworks\u27 Pictorial Qualities

Surface cleaning is a restoration process that involves the removal of dirt, grime, and discolored varnish from a damaged painting\u27s surface film, thereby presumably enhancing the visual clarity of its pictorial features and aesthetic effects. However, whether surface restoration really has these desired effects is an open question addressed in the present research. We report results of 2 studies, the first of which examined participants\u27 visual exploration (scanpath) using eye tracking of 10 prerestored paintings and their postrestored counterparts. Participants in both studies rated the paintings on items of the Information Rate Scale, a measure of a painting\u27s physical, structural, and content characteristics. Eye-tracking results show that the mean values for duration of the first fixation, total viewing time, total number of fixations, and coverage were all significantly greater for the restored versus unrestored images. Heat maps depicting participants\u27 combined data are compared for restoration effects. In the second study, significant differences were obtained between unrestored versus restored images for a number of Information Rate Scale items. These findings provide the first empirical evidence for the effects of restoration on the aesthetic experience of artworks

In Vitro Functional Characterization of BtuCD-F, the Escherichia coli ABC Transporter for Vitamin B_(12) Uptake

BtuCD is an ATP binding cassette (ABC) transporter that facilitates uptake of vitamin B_(12) into the cytoplasm of Escherichia coli. The crystal structures of BtuCD and its cognate periplasmic binding protein BtuF have been recently determined. We have now explored BtuCD-F function in vitro, both in proteoliposomes and in various detergents. BtuCD reconstituted into proteoliposomes has a significant basal ATP hydrolysis rate that is stimulated by addition of BtuF and inhibited by sodium ortho-vanadate. When using different detergents to solubilize BtuCD, the basal ATP hydrolysis rate, the ability of BtuF to stimulate hydrolysis, and the extent to which sodium ortho-vanadate inhibits ATP hydrolysis all vary significantly. Reconstituted BtuCD can mediate transport of vitamin B_(12) against a concentration gradient when coupled to ATP hydrolysis by BtuD in the liposome lumen and BtuF outside the liposomes. These in vitro studies establish the functional competence of the BtuCD and BtuF preparations used in the crystallographic analyses for both ATPase and transport activities. Furthermore, the tight binding of BtuF to BtuCD under the conditions studied suggests that the binding protein may not dissociate from the transporter during the catalytic cycle, which may be relevant to the mechanisms of other ABC transporter systems

A randomized controlled trial of a theoretically-based behavioral nutrition intervention for community elders: lessons learned from the Behavioral Nutrition Intervention for Community Elders Study.

Older adults with multiple comorbidities are often undernourished or at high risk for becoming so, especially after a recent hospitalization. Randomized controlled trials of effective, innovative interventions are needed to support evidence-based approaches for solving nutritional problems in this population. Self-management approaches where participants select their own behavioral goals can enhance success of interventions. The purpose of this study was to evaluate the feasibility and efficacy of a multilevel self-management intervention to improve nutritional status in a group of high-risk older adults. The Behavioral Nutrition Intervention for Community Elders (B-NICE) trial used a prospective randomized controlled design to determine whether the intervention, compared to standard care, maintained or increased caloric intake (depending on baseline body mass index) and, consequently, stabilized or increased body weight. Participants were 34 Medicare-eligible, age 65 years old or older, homebound adults who were consuming insufficient calories and/or had a history of weight loss ≥2.5% over 6 months. The intervention took place within participants' homes. Outcome measures, including energy intake (based on collection of three 24-hour dietary recalls) and body weights were assessed at baseline and at 60 days post randomization. The primary analyses included analyses of covariance and Pearson's χ(2). We hypothesized that the intervention would result in increased caloric intake and weight gain in underweight older adults and increased or stabilized caloric intake and weight for everyone else. The intervention was feasible; however, it did not result in differences between groups for desired outcomes of either caloric intake or body weight. Future interventions might either deliberately involve caregivers or reduce burden for both patients and caregivers

A randomized controlled trial of a theoretically-based behavioral nutrition intervention for community elders: lessons learned from the Behavioral Nutrition Intervention for Community Elders Study.

Older adults with multiple comorbidities are often undernourished or at high risk for becoming so, especially after a recent hospitalization. Randomized controlled trials of effective, innovative interventions are needed to support evidence-based approaches for solving nutritional problems in this population. Self-management approaches where participants select their own behavioral goals can enhance success of interventions. The purpose of this study was to evaluate the feasibility and efficacy of a multilevel self-management intervention to improve nutritional status in a group of high-risk older adults. The Behavioral Nutrition Intervention for Community Elders (B-NICE) trial used a prospective randomized controlled design to determine whether the intervention, compared to standard care, maintained or increased caloric intake (depending on baseline body mass index) and, consequently, stabilized or increased body weight. Participants were 34 Medicare-eligible, age 65 years old or older, homebound adults who were consuming insufficient calories and/or had a history of weight loss ≥2.5% over 6 months. The intervention took place within participants' homes. Outcome measures, including energy intake (based on collection of three 24-hour dietary recalls) and body weights were assessed at baseline and at 60 days post randomization. The primary analyses included analyses of covariance and Pearson's χ(2). We hypothesized that the intervention would result in increased caloric intake and weight gain in underweight older adults and increased or stabilized caloric intake and weight for everyone else. The intervention was feasible; however, it did not result in differences between groups for desired outcomes of either caloric intake or body weight. Future interventions might either deliberately involve caregivers or reduce burden for both patients and caregivers