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1.  Mapping the functional yeast ABC transporter interactome 
Nature chemical biology  2013;9(9):10.1038/nchembio.1293.
ABC transporters are a ubiquitous class of integral membrane proteins of immense clinical interest because of their strong association with human disease and pharmacology. To improve our understanding of these proteins, we used Membrane Yeast Two-Hybrid (MYTH) technology to map the protein interactome of all non-mitochondrial ABC transporters in the model organism Saccharomy cescerevisiae, and combined this data with previously reported yeast ABC transporter interactions in the BioGRID database to generate a comprehensive, integrated interactome. We show that ABC transporters physically associate with proteins involved in a surprisingly diverse range of functions. We specifically examine the importance of the physical interactions of ABC transporters in both the regulation of one another and in the modulation of proteins involved in zinc homeostasis. The interaction network presented here will be a powerful resource for increasing our fundamental understanding of the cellular role and regulation of ABC transporters.
doi:10.1038/nchembio.1293
PMCID: PMC3835492  PMID: 23831759
2.  People with limiting long-term conditions report poorer experiences and more problems with hospital care 
Background
Long-term conditions have a significant impact on individuals, their families, and the health service. As people with these conditions represent a high proportion of hospital admissions, investigating their experiences of inpatient care has become an important area of investigation. We conducted a secondary analysis of the NHS adult inpatient survey for England to compare the hospital experiences of three groups of patients: those without long-term conditions, those with a single long-term condition, and those with multiple long-term conditions. We were particularly interested in the extent to which these patients received self-management support from hospital staff, so we developed a brief summary tool drawn from salient questions in the survey to aid the comparison.
Methods
Analysis of data from the 2011 national adult inpatient survey (n = 65,134) to compare the experiences of three groups of patients: those with no limiting long-term conditions (No-LLTC), those with one limiting long-term condition (S-LLTC), and those with two or more limiting long-term conditions (M-LLTC). The main outcome measure was patients’ self-reports of their experience of inpatient care, including staff-patient interactions, information provision, involvement in decisions and support for self-care and overall ratings of care. A short form scale, the Oxford Patient Involvement and Experience scale (OxPIE) was developed from the adult inpatient survey and used to compare the groups using logistic regression.
Results
There were significant differences between the No-LLTC group in comparison to both the S-LLTC and M-LLTC groups. Patients with limiting long-term conditions reported significantly worse hospital experiences than those without, as measured by OxPIE: S-LLTC odds ratio = 1.23, 95% CI 1.03-1.48; M-LLTC odds ratio = 1.64, 95% CI 1.19 – 2.26. Responses to a single global rating question were more positive but not strongly correlated with OxPIE.
Conclusions
Patients with LLTCs were more critical of their inpatient care than those with no LLTCs. Those with more than one long-term condition reported worse experiences than those with a single limiting condition. Simple rating questions may not be sufficiently sensitive to reflect important aspects of patients’ experience.
doi:10.1186/1472-6963-14-33
PMCID: PMC3937147  PMID: 24456971
Patient reported experience; Questionnaire development; Long term conditions; Questionnaire survey; Patient satisfaction
3.  The MoxR ATPase RavA and Its Cofactor ViaA Interact with the NADH:Ubiquinone Oxidoreductase I in Escherichia coli 
PLoS ONE  2014;9(1):e85529.
MoxR ATPases are widespread throughout bacteria and archaea. The experimental evidence to date suggests that these proteins have chaperone-like roles in facilitating the maturation of dedicated protein complexes that are functionally diverse. In Escherichia coli, the MoxR ATPase RavA and its putative cofactor ViaA are found to exist in early stationary-phase cells at 37°C at low levels of about 350 and 90 molecules per cell, respectively. Both proteins are predominantly localized to the cytoplasm, but ViaA was also unexpectedly found to localize to the cell membrane. Whole genome microarrays and synthetic lethality studies both indicated that RavA-ViaA are genetically linked to Fe-S cluster assembly and specific respiratory pathways. Systematic analysis of mutant strains of ravA and viaA indicated that RavA-ViaA sensitizes cells to sublethal concentrations of aminoglycosides. Furthermore, this effect was dependent on RavA's ATPase activity, and on the presence of specific subunits of NADH:ubiquinone oxidoreductase I (Nuo Complex, or Complex I). Importantly, both RavA and ViaA were found to physically interact with specific Nuo subunits. We propose that RavA-ViaA facilitate the maturation of the Nuo complex.
doi:10.1371/journal.pone.0085529
PMCID: PMC3893208  PMID: 24454883
4.  Rhythmic actomyosin-driven contractions induced by sperm entry predict mammalian embryo viability 
Nature Communications  2011;2:417-.
Fertilization-induced cytoplasmic flows are a conserved feature of eggs in many species. However, until now the importance of cytoplasmic flows for the development of mammalian embryos has been unknown. Here, by combining a rapid imaging of the freshly fertilized mouse egg with advanced image analysis based on particle image velocimetry, we show that fertilization induces rhythmical cytoplasmic movements that coincide with pulsations of the protrusion forming above the sperm head. We find that these movements are caused by contractions of the actomyosin cytoskeleton triggered by Ca2+ oscillations induced by fertilization. Most importantly, the relationship between the movements and the events of egg activation makes it possible to use the movements alone to predict developmental potential of the zygote. In conclusion, this method offers, thus far, the earliest and fastest, non-invasive way to predict the viability of eggs fertilized in vitro and therefore can potentially improve greatly the prospects for IVF treatment.
Cytoplasmic flows—the movement of cytoplasmic material—can be detected following the fertilization of an egg by a sperm in many species. In this study, rhythmic cytoplasmic flows are shown to be induced in mice by calcium-induced cytoskeleton contractions which could be used to predict the successful outcome of fertilization.
doi:10.1038/ncomms1424
PMCID: PMC3265380  PMID: 21829179
5.  Ribosome-Dependent ATPase Interacts with Conserved Membrane Protein in Escherichia coli to Modulate Protein Synthesis and Oxidative Phosphorylation 
PLoS ONE  2011;6(4):e18510.
Elongation factor RbbA is required for ATP-dependent deacyl-tRNA release presumably after each peptide bond formation; however, there is no information about the cellular role. Proteomic analysis in Escherichia coli revealed that RbbA reciprocally co-purified with a conserved inner membrane protein of unknown function, YhjD. Both proteins are also physically associated with the 30S ribosome and with members of the lipopolysaccharide transport machinery. Genome-wide genetic screens of rbbA and yhjD deletion mutants revealed aggravating genetic interactions with mutants deficient in the electron transport chain. Cells lacking both rbbA and yhjD exhibited reduced cell division, respiration and global protein synthesis as well as increased sensitivity to antibiotics targeting the ETC and the accuracy of protein synthesis. Our results suggest that RbbA appears to function together with YhjD as part of a regulatory network that impacts bacterial oxidative phosphorylation and translation efficiency.
doi:10.1371/journal.pone.0018510
PMCID: PMC3083400  PMID: 21556145
6.  Comparison of patients' assessments of the quality of stroke care with audit findings 
Quality & Safety in Health Care  2007;16(6):450-455.
Objective
To determine the extent of correlation between stroke patients' experiences of hospital care with the quality of services assessed in a national audit.
Methods
Patients' assessments of their care derived from survey data were linked to data obtained in the National Sentinel Stroke Audit 2004 for 670 patients in 51 English NHS trusts. A measure of patients' experience of hospital stroke care was derived by summing responses to 31 survey items and grouping these into three broad concept domains: quality of care; information; and relationships with staff. Audit data were extracted from hospital admissions data and management information to assess the organisation of services, and obtained retrospectively from patient records to evaluate the delivery of care. Patient survey responses were compared with audit measures of organisation of care and compliance with clinical process standards.
Results
Patient experience scores were positively correlated with clinicians' assessment of the organisational quality of stroke care, but were largely unrelated to clinical process standards. Responses to individual questions regarding communication about diagnosis revealed a discrepancy between clinicians' and patients' reports.
Conclusions
Better organised stroke care is associated with more positive patient experiences. Examining areas of disparity between patients' and clinicians' reports is important for understanding the complex nature of healthcare and for identifying areas for quality improvement. Future evaluations of the quality of stroke services should include a validated patient experience survey in addition to audit of clinical records.
doi:10.1136/qshc.2006.022079
PMCID: PMC2653182  PMID: 18055890

Results 1-6 (6)