bluuebunny/crossref_metadata_2025_split huggingface dataset:
Liver microsomal lipid enhances the activity and redox coupling of colocalized cytochrome P450 reductase‐cytochrome P450 3A4 in nanodiscs
Authors: Liu Kang‐Cheng , Hughes John M. X. , Hay Sam , Scrutton Nigel S. 
Published: June 2017

The haem‐containing mono‐oxygenase cytochrome P450 3A4 (CYP3A4) and its redox partner NADPH‐dependent cytochrome P450 oxidoreductase (CPR) are among the most important enzymes in human liver for metabolizing drugs and xenobiotic compounds. They are membrane‐bound in the endoplasmic reticulum (ER). How ER colocalization and the complex ER phospholipid composition influence enzyme activity are not well understood. CPR and CYP3A4 were incorporated into phospholipid bilayer nanodiscs, both singly, and together in a 1 : 1 ratio, to investigate the significance of membrane insertion and the influence of varying membrane composition on steady‐state reaction kinetics. Reaction kinetics were analysed using a fluorimetric assay with 7‐benzyloxyquinoline as substrate for CYP3A4. Full activity of the mono‐oxygenase system, with electron transfer from NADPH via CPR, could only be reconstituted when CPR and CYP3A4 were colocalized within the same nanodiscs. No activity was observed when CPR and CYP3A4 were each incorporated separately into nanodiscs then mixed together, or when soluble forms of CPR were mixed with preassembled CYP3A4‐nanodiscs. Membrane integration and colocalization are therefore essential for electron transfer. Liver microsomal lipid had an enhancing effect compared with phosphatidylcholine on the activity of CPR alone in nanodiscs, and a greater enhancing effect on the activity of CPR‐CYP3A4 nanodisc complexes, which was not matched by a phospholipid mixture designed to mimic the ER composition. Furthermore, liver lipid enhanced redox coupling within the system. Thus, natural ER lipids possess properties or include components important for enhanced catalysis by CPR‐CYP3A4 nanodisc complexes. Our findings demonstrate the importance of using natural lipid preparations for the detailed analysis of membrane protein activity.
Lipid interactions modulate the structural and antigenic properties of the C‐terminal domain of the malaria antigen merozoite surface protein 2
Authors: Das Sreedam C. , Morales Rodrigo A.V. , Seow Jeffrey , Krishnarjuna Bankala , Dissanayake Ravindu , Anders Robin F. , MacRaild Christopher A. , Norton Raymond S. 
Published: June 2017

Merozoite surface protein 2 (MSP2) is a highly abundant, GPI‐anchored antigen on the malaria parasite Plasmodium falciparum. MSP2 induces an immune response in the context of natural infections and vaccine trials, and these responses are associated with protection from parasite infection. Recombinant MSP2 is highly disordered in solution but antigenic analyses suggest that it is more ordered on the merozoite surface. We have shown previously that the interaction of recombinant full‐length MSP2 with lipid surfaces induces a conformational change in the conserved N‐terminal region of MSP2, which contributes to epitope masking in this region. To explore the impacts of lipid interactions on the conformation and antigenicity of the conserved C‐terminal region of MSP2, a construct corresponding to this domain, MSP2172–221, was designed. NMR studies indicate that many residues in MSP2172–221 interact with DPC micelles, including some in epitopes recognised by C‐terminal‐specific monoclonal antibodies, but, in contrast to the MSP2 N‐terminus, there is no indication of stable helical conformation. The binding affinities of a panel of monoclonal antibodies indicate that MSP2172–221 is antigenically similar to full‐length MSP2 and show that liposome conjugation alters the antigenicity in a manner that may mimic native MSP2 on the merozoite surface. These findings highlight the impact of lipid interactions on the conformation and antigenicity of MSP2172–221 and will assist in the design of recombinant MSP2 immunogens for use as malaria vaccine candidates.DatabasesResonance assignments are available in the BioMagResBank (BMRB) database under the accession number 27134.
Towards improved ODS steels: A comparative high‐temperature low‐cycle fatigue study
Authors: Chauhan A. , Walter M. , Aktaa J. 
Published: June 2017

AbstractWithin the frame of this work, the mechanical behaviour of a bimodal ferritic 12Cr‐ODS steel as well as of a ferritic‐martensitic 9Cr‐ODS steel under alternating load conditions was investigated. In general, strain‐controlled low‐cycle fatigue tests at 550°C and 650°C revealed similar cyclic stress response. At elevated temperatures, the two steels manifest transitional stages, ie, cyclic softening and/or hardening corresponding to the small fraction of the cyclic life, which is followed by a linear cyclic softening stage that occupies the major fraction of the cyclic life until failure. However, it is clearly seen that the presence of the nano‐sized oxide particles is certainly beneficial, as the degree of cyclic softening is significantly reduced compared with non‐ODS steels. Besides, it is found that both applied strain amplitude and testing temperature show a strong influence on the cyclic stress response. It is observed that the degree of linear cyclic softening in both steels increases with increasing strain amplitude and decreasing test temperature. The effect of temperature on inelastic strain and hence lifetime becomes more pronounced with decreasing applied strain amplitude. When analysing the lifetime behaviour of both ODS steels in terms of inelastic strain energy calculations, it is found that comparable inelastic strain energies lead to similar lifetimes at 550°C. At 650°C, however, the higher inelastic strain energies of 12Cr‐ODS steel result in significant lower lifetimes compared with those of the 9Cr‐ODS steel. The strong degradation of the cyclic properties of the 12Cr‐ODS steel is obviously linked to the fact that the initial hardening response appears significantly more pronounced at 650°C than at 550°C. Finally, the obtained results depict that the 9Cr‐ODS steel offers higher number of cycles to failure at 650°C, compared with other novel ODS steels described in literature.
Crack incubation in shot peened AA7050 and mechanism for fatigue enhancement
Authors: Chadwick Daniel J. , Ghanbari Siavash , Bahr David F. , Sangid Michael D. 
Published: June 2017

AbstractShot peening is a dynamic cold‐working process involving the impingement of peening media onto a substrate surface. Shot peening is commonly used as a surface treatment technique within the aerospace industry during manufacturing to improve fatigue performance of structural components. The compressive residual stress induced during shot peening results in fatigue crack growth retardation, improving the performance of shot‐peened components. However, shot peening is a compromise between the benefit of inducing a compressive residual stress and causing detrimental surface damage. Because of the relatively soft nature of AA7050‐T7451, shot peening can result in cracking of the constituent precipitate particles, creating an initial damage state. The aim of this paper is to understand the balance and fundamentals of these competing phenomena through a comparative study throughout the fatigue lifecycle of baseline versus shot‐peened AA7050‐T7451. Microstructure and surface topology characterization and comparison of the baseline and shot‐peened AA7050‐T7451 has been performed using scanning electron microscopy, electron backscatter diffraction, energy dispersive spectroscopy, and optical profilometry techniques. A residual stress analysis through interrupted fatigue of the baseline and shot‐peened AA7050‐T7451 was completed using a combination of X‐ray diffraction and nanoindentation. The fatigue life performance of the baseline versus shot‐peened material has been evaluated, including crack initiation and propagation. Subsurface particles crack upon shot peening but did not incubate into the matrix during fatigue loading, presumably due to the compressive residual stress field. In the baseline samples, the particles were initially intact, but upon fatigue loading, crack nucleation was observed in the particles, and these cracks incubated into the matrix. In damage tolerant analysis, an initial defect size is needed for lifetime assessment, which is often difficult to determine, leading to overly conservative evaluations. This work provides a critical assessment of the mechanism for shot peening enhancement for fatigue performance and quantifies how incubation of a short crack is inhibited from an initially cracked particle into the matrix within a residual stress field.
Direct and indirect effects of predatory young‐of‐year fishes in a dryland river food web
Authors: Krabbenhoft Corey A. , Burdett Ayesha S. , Turner Thomas F. 
Published: June 2017

Summary

Young‐of‐year (YOY) fishes are sometimes numerically dominant vertebrate consumers in many large river systems, but their effects as predators are not as well understood as those of adult fishes. We predicted that YOY fishes influence community composition and abundance of invertebrate prey. Predation effects could be especially important in recruitment‐driven dryland river systems, where YOY fishes seasonally comprise a large portion of overall fish biomass.

We conducted a mesocosm experiment to quantify effects of YOY fishes on trophic dynamics and interactions with environmental factors in a dryland river food web. We manipulated presence of YOY fishes (an assemblage of cypriniform species) and supplemental allochthonous carbon (LEAF treatments) in 24 mesocosms, and measured invertebrate abundance and diversity over 6 weeks. Experimental conditions mimicked a seasonal river drying regime that occurs during YOY fish growth. Seasonal drying in the Rio Grande frequently results in isolated pools with altered habitat complexity and riparian connectivity.

Fishes exerted direct top‐down control of invertebrate assemblage composition through differential prey selection, and indirect control mediated by non‐lethal responses of invertebrates to predatory fishes. We observed enhanced water clarity in LEAF treatments associated with greater prey selectivity in fishes, presumably through enhanced visual feeding. Stable isotope analysis (C and N) was used to measure indirect impacts of YOY fishes on invertebrate prey items. YOY fishes caused a significant decrease in “isotopic niche breadth” among invertebrate taxa, suggesting that fish predators limit foraging opportunities for these consumers. However, allochthonous carbon sources were predominant in invertebrate diets in all LEAF treatments, suggesting consumer access to more biologically available autochthonous production is limited by factors other than fish predation.

Although the roles of abiotic drivers and adult fishes in determining food web structure have received more attention, our results indicate that YOY fishes exert biologically relevant top‐down control of invertebrate assemblage composition and trophic complexity in dryland river ecosystems against a backdrop of substantial changes in carbon availability and abiotic conditions (e.g. water quality and habitat volume) over the growing season.
Groundwater Quality: Analysis of Its Temporal and Spatial Variability in a Karst Aquifer
Authors: Pacheco Castro Roger , Pacheco Ávila Julia , Ye Ming , Cabrera Sansores Armando 
Published: June 2017

AbstractThis study develops an approach based on hierarchical cluster analysis for investigating the spatial and temporal variation of water quality governing processes. The water quality data used in this study were collected in the karst aquifer of Yucatan, Mexico, the only source of drinking water for a population of nearly two million people. Hierarchical cluster analysis was applied to the quality data of all the sampling periods lumped together. This was motivated by the observation that, if water quality does not vary significantly in time, two samples from the same sampling site will belong to the same cluster. The resulting distribution maps of clusters and box‐plots of the major chemical components reveal the spatial and temporal variability of groundwater quality. Principal component analysis was used to verify the results of cluster analysis and to derive the variables that explained most of the variation of the groundwater quality data. Results of this work increase the knowledge about how precipitation and human contamination impact groundwater quality in Yucatan. Spatial variability of groundwater quality in the study area is caused by: a) seawater intrusion and groundwater rich in sulfates at the west and in the coast, b) water rock interactions and the average annual precipitation at the middle and east zones respectively, and c) human contamination present in two localized zones. Changes in the amount and distribution of precipitation cause temporal variation by diluting groundwater in the aquifer. This approach allows to analyze the variation of groundwater quality controlling processes efficiently and simultaneously.
Gamma‐Aminobutyric Acid (Gaba) Receptors Rho (Gabrr) Gene Polymorphisms and Risk for Migraine
Authors: García‐Martín Elena , Martínez Carmen , Serrador Mercedes , Alonso‐Navarro Hortensia , Navacerrada Francisco , Esguevillas Gara , García‐Albea Esteban , Agúndez José A. G. , Jiménez‐Jiménez Félix Javier 
Published: June 2017

Background/objectivesThe possible role of gammaaminobutyric acid (GABA) in the pathogenesis of migraine has been suggested by a number of biochemical, pharmacological, neurophysiological and experimental data. We investigated the possible association between the most common single nucleotide polymorphisms (SNPs) in the GABA receptor rho1, 2, and 3 genes (GABRR1, GABRR2, and GABRR3) and the risk of developing migraine.MethodsThe frequency of GABRR1 rs12200969, GABRR1 rs1186902, GABRR2 rs282129, and GABRR3 rs832032 genotypes and allelic variants were studied in a case‐control association study involving 197 patients with migraine and 278 healthy controls by means of a TaqMan‐based qPCR Assay. We also studied the possible influence of gender, age at onset of migraine, positive family history of migraine, presence or absence of aura, and triggering of migraine by ethanol on the frequency of the genotypes.ResultsThe frequencies of the genotypes and allelic variants of the 4 SNPs were similar in migraine patients and controls. Gender, positive family history of migraine, presence or absence of aura, and triggering of migraine attacks by ethanol did not influence the frequency of these genotypes. Carriers of the minor allele of the rs1186902 SNP showed a trend towards later onset of migraine.ConclusionThe most common polymorphisms in the GABRR genes seemed to be not associated with the risk for migraine in Caucasian Spanish people, although one of them (GABRR1 rs1186902) shows a statistically significant association with the age of onset of migraine.
Prevalence of Restless Legs Syndrome in Migraine Patients: A Case‐Control Study. Analysis of Risk Factors for Restless Legs Syndrome in Migraine Patients
Authors: Valente Mariarosaria , Janes Francesco , Russo Valentina , Fontana Augusto , Travanut Alessia , Sommaro Martina , Canal Giessica , Gentile Carolina , Luigi Gigli Gian 
Published: June 2017

BackgroundRestless legs syndrome (RLS) is a sensorimotor disorder. It can be idiopathic, associated to other diseases or to pharmacologic treatments. RLS has been reported to occur more frequently in migraine patients, but a clear pathogenetic link seems still under debate. We aimed to evaluate RLS prevalence in migraine, impact on sleep quality and the main clinical determinants of this association.MethodsMigraine patients and age‐ and sex‐matched controls were enrolled from 1st January 2011 to 30th December 2012. Migraine and RLS diagnosis complied with already published clinical criteria. Medical and pharmacological histories, as well as structured questionnaires were collected.ResultsRLS was found in 29/180 (16.1%) patients and 11/180 (6.1%) controls. The odds ratio (OR) for RLS was 2.95 (CI 95%, 1.42‐6.11). Among migraine patients, after adjustment for possible confounding factors, familial history (OR 3.863, CI 1.076‐13.873), and serotoninergic overload (OR 3.654, CI 1.347‐9.916) were significantly associated with RLS occurrence. Pittsburgh Sleep Quality Index score was higher in migraine patients with RLS than in subjects without RLS.ConclusionsThe confirmed association between migraine and RLS might be because of familial predisposition and to serotoninergic drugs effect, possibly interfering with the balance between dopaminergic and serotoninergic pathways.
A qualitative formative evaluation of a patient‐centred patient safety intervention delivered in collaboration with hospital volunteers
Authors: Louch Gemma , O'Hara Jane , Mohammed Mohammed A. 
Published: June 2017

AbstractBackgroundEvidence suggests that patients can meaningfully feed back to healthcare providers about the safety of their care. The PRASE (Patient Reporting and Action for a Safe Environment) intervention provides a way to systematically collect feedback from patients to support service improvement. The intervention is being implemented in acute care settings with patient feedback collected by hospital volunteers for the first time.ObjectiveTo undertake a formative evaluation which explores the feasibility and acceptability of the PRASE intervention delivered in collaboration with hospital volunteers from the perspectives of key stakeholders.DesignA qualitative evaluation design was adopted across two acute NHS trusts in the UK between July 2014 and November 2015. We conducted five focus groups with hospital volunteers (n=15), voluntary services and patient experience staff (n=3) and semi‐structured interviews with ward staff (n=5). Data were interpreted using framework analysis.ResultsAll stakeholders were positive about the PRASE intervention as a way to support service improvement, and the benefits of involving volunteers. Volunteers felt adequate training and support would be essential for retention. Staff concentrated on the infrastructure needed for implementation and raised concerns around sustainability. Findings were fed back to the implementation team to support revisions to the intervention moving into the subsequent summative evaluation phase.ConclusionAlthough there are concerns regarding sustainability in practice, the PRASE intervention delivered in collaboration with hospital volunteers is a promising approach to collect patient feedback for service improvement.
Feedback preferences of patients, professionals and health insurers in integrated head and neck cancer care
Authors: van Overveld Lydia F. J. , Takes Robert P. , Vijn Thomas W. , Braspenning Jozé C. C. , de Boer Jan P. , Brouns John J. A. , Bun Rolf J. , van Dijk Boukje A. C. , Dortmans Judith A. W. F. , Dronkers Emilie A. C. , van Es Robert J. J. , Hoebers Frank J. P. , Kropveld Arvid , Langendijk Johannes A. , Langeveld Ton P. M. , Oosting Sjoukje F. , Verschuur Hendrik P. , de Visscher Jan G. A. M. , van Weert Stijn , Merkx Matthias A. W. , Smeele Ludi E. , Hermens Rosella P. M. G. 
Published: June 2017

AbstractBackgroundAudit and feedback on professional practice and health care outcomes are the most often used interventions to change behaviour of professionals and improve quality of health care. However, limited information is available regarding preferred feedback for patients, professionals and health insurers.ObjectiveInvestigate the (differences in) preferences of receiving feedback between stakeholders, using the Dutch Head and Neck Audit as an example.MethodsA total of 37 patients, medical specialists, allied health professionals and health insurers were interviewed using semi‐structured interviews. Questions focussed on: “Why,” “On what aspects” and “How” do you prefer to receive feedback on professional practice and health care outcomes?ResultsAll stakeholders mentioned that feedback can improve health care by creating awareness, enabling self‐reflection and reflection on peers or colleagues, and by benchmarking to others. Patients prefer feedback on the actual professional practice that matches the health care received, whereas medical specialists and health insurers are interested mainly in health care outcomes. All stakeholders largely prefer a bar graph. Patients prefer a pie chart for patient‐reported outcomes and experiences, while Kaplan‐Meier survival curves are preferred by medical specialists. Feedback should be simple with firstly an overview, and 1‐4 times a year sent by e‐mail. Finally, patients and health professionals are cautious with regard to transparency of audit data.ConclusionsThis exploratory study shows how feedback preferences differ between stakeholders. Therefore, tailored reports are recommended. Using this information, effects of audit and feedback can be improved by adapting the feedback format and contents to the preferences of stakeholders.
How does the side‐effect information in patient information leaflets influence peoples’ side‐effect expectations? A cross‐sectional national survey of 18‐ to 65‐year‐olds in England
Authors: Webster Rebecca K. , Weinman John , Rubin G. James 
Published: June 2017

AbstractObjectivesTo establish how the terms recommended by the European Commission to describe side‐effect risk in patient information leaflets (PILs) influences expectations of side‐effects and to identify factors associated with these side‐effect expectations.DesignA cross‐sectional online survey was carried out by a market research company.SettingData were collected in England between 18th March and 1st April 2016.ParticipantsA total of 1003 adults aged between 18 and 65. Main outcome measures: Self‐reported expectation that the described side‐effects would affect participants if they took the medicine, measured on a likelihood scale from 1 (very unlikely) to 5 (very likely).ResultsParticipants formed high expectations of side‐effects for “very common” and “common” side‐effects, with 51.9% and 45.0% of participants rating these as “very likely” or “likely” to happen to them, respectively. This fell to 8.1% for “uncommon,” 5.8% for “rare” and 4.1% for “very rare.” For each descriptor, higher expectations of side‐effects were more associated with women or being from an ethnic minority, or having less education, a household illness, high perceived sensitivity to medicines or negative beliefs about medicines.DiscussionThe current use of verbal descriptors to communicate side‐effect risk in PILs leads to high side‐effect expectations. These expectations could contribute to nocebo‐induced medication side‐effects experienced by patients. Additional work is required to identify ways to improve the way risk information is conveyed in PILs.