bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tricellular Tight Junction Protein Tricellulin Is Targeted by the Enteropathogenic Escherichia coli Effector EspG1, Leading to Epithelial Barrier Disruption
Authors: Morampudi Vijay , Graef Franziska A. , Stahl Martin , Dalwadi Udit , Conlin Victoria S. , Huang Tina , Vallance Bruce A. , Yu Hong B. , Jacobson Kevan 
Published: October 2016

ABSTRACT

Enteropathogenic
Escherichia coli
(EPEC)-induced diarrhea is often associated with disruption of intestinal epithelial tight junctions. Although studies have shown alterations in the expression and localization of bicellular tight junction proteins during EPEC infections, little is known about whether tricellular tight junction proteins (tTJs) are affected. Using Caco-2 cell monolayers, we investigated if EPEC is capable of targeting the tTJ protein tricellulin. Our results demonstrated that at 4 h postinfection, EPEC induced a significant reduction in tricellulin levels, accompanied by a significant loss of transepithelial resistance (TEER) and a corresponding increase in paracellular permeability. Conversely, cells overexpressing tricellulin were highly resistant to EPEC-induced barrier disruption. Confocal microscopy revealed the distribution of tricellulin into the plasma membrane of infected epithelial cells and confirmed the localization of EPEC aggregates in close proximity to tTJs. Moreover, infections with EPEC strains lacking genes encoding specific type III secreted effector proteins demonstrated a crucial role for the effector EspG1 in modulating tricellulin expression. Complementation studies suggest that the EspG-induced depletion of tricellulin is microtubule dependent. Overall, our results show that EPEC-induced epithelial barrier dysfunction is mediated in part by EspG1-induced microtubule-dependent depletion of tricellulin.
Null Mutations of Group A Streptococcus Orphan Kinase RocA: Selection in Mouse Infection and Comparison with CovS Mutations in Alteration of
In Vitro
and
In Vivo
Protease SpeB Expression and Virulence
Authors: Feng Wenchao , Minor Dylan , Liu Mengyao , Li Jinquan , Ishaq Suzanne L. , Yeoman Carl , Lei Benfang 
Published: October 2016

ABSTRACT

Group A
Streptococcus
(GAS) acquires mutations of the virulence regulator CovRS in human and mouse infections, and these mutations result in the upregulation of virulence genes and the downregulation of the protease SpeB. To identify
in vivo
mutants with novel phenotypes, GAS isolates from infected mice were screened by enzymatic assays for SpeB and the platelet-activating factor acetylhydrolase Sse, and a new type of variant that had enhanced Sse expression and normal levels of SpeB production was identified (the variants had a phenotype referred to as enhanced Sse activity [Sse
A+
] and normal SpeB activity [SpeB
A+
]). Sse
A+
SpeB
A+
variants had transcript levels of CovRS-controlled virulence genes comparable to those of a
covS
mutant but had no
covRS
mutations. Genome resequencing of an Sse
A+
SpeB
A+
isolate identified a C605A nonsense mutation in orphan kinase gene
rocA
, and 6 other Sse
A+
SpeB
A+
isolates also had nonsense mutations or small indels in
rocA
. RocA and CovS mutants had similar levels of enhancement of the expression of CovRS-controlled virulence genes at the exponential growth phase; however, mutations of RocA but not mutations of CovS did not result in the downregulation of
speB
transcription at stationary growth phase or in subcutaneous infection of mice. GAS with RocA and CovS mutations caused greater enhancement of the expression of
hasA
than
spyCEP
in mouse skin infection than wild-type GAS did. RocA mutants ranked between wild-type GAS and CovS mutants in skin invasion, inhibition of neutrophil recruitment, and virulence in subcutaneous infection of mice. Thus, GAS RocA mutants can be selected in subcutaneous infections in mice and exhibit gene expression patterns and virulences distinct from those of CovS mutants. The findings provide novel information for understanding GAS fitness mutations
in vivo
, virulence gene regulation,
in vivo
gene expression, and virulence.
Suppressor Mutations LinkinggpsBwith the First Committed Step of Peptidoglycan Biosynthesis in Listeria monocytogenes
Authors: Rismondo Jeanine , Bender Jennifer K. , Halbedel Sven 
Published: October 2016

ABSTRACTThe cell division protein GpsB is a regulator of the penicillin binding protein A1 (PBP A1) in the Gram-positive human pathogenListeria monocytogenes. Penicillin binding proteins mediate the last two steps of peptidoglycan biosynthesis as they polymerize and cross-link peptidoglycan strands, the main components of the bacterial cell wall. It is not known what other processes are controlled by GpsB.L. monocytogenesgpsBmutants are unable to grow at 42°C, but we observed that spontaneous suppressors correcting this defect arise on agar plates with high frequency. We here describe a first set ofgpsBsuppressors that mapped to theclpCandmurZgenes. While ClpC is the ATPase component of the Clp protease, MurZ is a paralogue of the listerial UDP–N-acetylglucosamine (UDP-GlcNAc) 1-carboxyvinyltransferase MurA. Both enzymes catalyze the enolpyruvyl transfer from phosphoenolpyruvate to UDP-GlcNAc, representing the first committed step of peptidoglycan biosynthesis. We confirmed that clean deletion of theclpCormurZgene suppressed the ΔgpsBphenotype. It turned out that the absence of either gene leads to accumulation of MurA, and we show that artificial overexpression of MurA alone was sufficient for suppression. Inactivation of other UDP-GlcNAc-consuming pathways also suppressed the heat-sensitive growth of the ΔgpsBmutant, suggesting that an increased influx of precursor molecules into peptidoglycan biosynthesis can compensate for the lack of GpsB. Our results support a model according to which PBP A1 becomes misregulated and thus toxic in the absence of GpsB due to unproductive consumption of cell wall precursor molecules.IMPORTANCEThe late cell division protein GpsB is important for cell wall biosynthesis in Gram-positive bacteria. GpsB of the human pathogenL. monocytogenesinteracts with one of the key enzymes of this pathway, penicillin binding protein A1 (PBP A1), and influences its activity. PBP A1 catalyzes the last two steps of cell wall biosynthesis, but it is unknown how GpsB controls PBP A1. We observed that aL. monocytogenesgpsBmutant forms spontaneous suppressors and have mapped their mutations to genes mediating and influencing the first step of cell wall biosynthesis, likely stimulating the influx of metabolites into this pathway. We assume that GpsB is important to ensure productive incorporation of cell wall precursors into the peptidoglycan sacculus by PBP A1.
Genes Required for Bacillus anthracis Secondary Cell Wall Polysaccharide Synthesis
Authors: Oh So-Young , Lunderberg J. Mark , Chateau Alice , Schneewind Olaf , Missiakas Dominique 
Published: October 2016

ABSTRACT

The secondary cell wall polysaccharide (SCWP) is thought to be essential for vegetative growth and surface (S)-layer assembly in
Bacillus anthracis
; however, the genetic determinants for the assembly of its trisaccharide repeat structure are not known. Here, we report that WpaA (BAS0847) and WpaB (BAS5274) share features with membrane proteins involved in the assembly of O-antigen lipopolysaccharide in Gram-negative bacteria and propose that WpaA and WpaB contribute to the assembly of the SCWP in
B. anthracis
. Vegetative forms of the
B. anthracis wpaA
mutant displayed increased lengths of cell chains, a cell separation defect that was attributed to mislocalization of the S-layer-associated murein hydrolases BslO, BslS, and BslT. The
wpaB
mutant was defective in vegetative replication during early logarithmic growth and formed smaller colonies. Deletion of both genes,
wpaA
and
wpaB
, did not yield viable bacilli, and when depleted of both
wpaA
and
wpaB
,
B. anthracis
could not maintain cell shape, support vegetative growth, or assemble SCWP. We propose that WpaA and WpaB fulfill overlapping glycosyltransferase functions of either polymerizing repeat units or transferring SCWP polymers to linkage units prior to LCP-mediated anchoring of the polysaccharide to peptidoglycan.

IMPORTANCE
The secondary cell wall polysaccharide (SCWP) is essential for
Bacillus anthracis
growth, cell shape, and division. SCWP is comprised of trisaccharide repeats (→4)-β-ManNAc-(1→4)-β-GlcNAc-(1→6)-α-GlcNAc-(1→) with α-Gal and β-Gal substitutions; however, the genetic determinants and enzymes for SCWP synthesis are not known. Here, we identify WpaA and WpaB and report that depletion of these factors affects vegetative growth, cell shape, and S-layer assembly. We hypothesize that WpaA and WpaB are involved in the assembly of SCWP prior to transfer of this polymer onto peptidoglycan.
Inflammation—a Critical Appreciation of the Role of Myeloid Cells
Authors: Iqbal Asif J. , Fisher Edward A. , Greaves David R. 
Published: October 2016

ABSTRACT
What is inflammation’s big idea? In this brief overview of the role of myeloid cells in inflammation, we will critically discuss what drives the initiation, amplification, and resolution of inflammation in different anatomical sites in response to different pathological stimuli. It can be argued that we have a good understanding of the basic principles that underlie myeloid cell activation and the mobilization of innate immune cells to sites of injury and infection in acute inflammation. The challenge now for inflammation biologists is to understand how resolution of this normal physiological response goes wrong in hyperacute and chronic inflammation. A better understanding of how inflammation is regulated will allow us to develop new anti-inflammatory drugs that will reduce the burden of inflammatory disease without compromising the patient’s immune defenses against infectious disease. Ideally such drugs should encourage a return to homeostasis and enhance tissue repair processes.
Regulatory Issues Associated with Preharvest Food Safety: European Union Perspective
Authors: Alban Lis 
Published: October 2016

ABSTRACT

Free movement of safe and wholesome food is an essential aspect of any society. This article contains an updated description of the regulatory issues associated with preharvest food safety within the European Union.
Salmonella
,
Campylobacter
,
Trichinella
, antimicrobial resistance, and bovine spongiform encephalopathy are dealt with in detail. Moreover,
Cysticercus bovis
/
Taenia saginata
,
Toxoplasma
,
Yersinia
, verotoxigenic/shigatoxigenic
Escherichia coli
,
Listeria
, and foodborne viruses are briefly covered. The article describes how the focus in the European Union is changing to involve a supply chain view with a focus on cost-effectiveness. The precautionary principle—as well as the use of private standards as an instrument to ensure compliance—is dealt with. In addition, actions in the pipeline are presented and discussed.
Cost-effectiveness of community versus hospital eye service follow-up for patients with quiescent treated age-related macular degeneration alongside the ECHoES randomised trial
Authors: Violato M , Dakin H , Chakravarthy U , Reeves B C , Peto T , Hogg R E , Harding S P , Scott L J , Taylor J , Cappel-Porter H , Mills N , O'Reilly D , Rogers C A , Wordsworth S 
Published: October 2016

ObjectivesTo assess the cost-effectiveness of optometrist-led follow-up monitoring reviews for patients with quiescent neovascular age-related macular degeneration (nAMD) in community settings (including high street opticians) compared with ophthalmologist-led reviews in hospitals.DesignA model-based cost-effectiveness analysis with a 4-week time horizon, based on a ‘virtual’ non-inferiority randomised trial designed to emulate a parallel group design.SettingA virtual internet-based clinical assessment, conducted at community optometry practices, and hospital ophthalmology clinics.ParticipantsOphthalmologists with experience in the age-related macular degeneration service; fully qualified optometrists not participating in nAMD shared care schemes.InterventionsThe participating optometrists and ophthalmologists classified lesions from vignettes and were asked to judge whether any retreatment was required. Vignettes comprised clinical information, colour fundus photographs and optical coherence tomography images. Participants' classifications were validated against experts' classifications (reference standard). Resource use and cost information were attributed to these retreatment decisions.Main outcome measuresCorrect classification of whether further treatment is needed, compared with a reference standard.ResultsThe mean cost per assessment, including the subsequent care pathway, was £411 for optometrists and £397 for ophthalmologists: a cost difference of £13 (95% CI −£18 to £45). Optometrists were non-inferior to ophthalmologists with respect to the overall percentage of lesions correctly assessed (difference −1.0%; 95% CI −4.5% to 2.5%).ConclusionsIn the base case analysis, the slightly larger number of incorrect retreatment decisions by optometrists led to marginally and non-significantly higher costs. Sensitivity analyses that reflected different practices across eye hospitals indicate that shared care pathways between optometrists and ophthalmologists can be identified which may reduce demands on scant hospital resources, although in light of the uncertainty around differences in outcome and cost it remains unclear whether the differences between the 2 care pathways are significant in economic terms.Trial registration numberISRCTN07479761; Pre-results.
Experiences and explanations of mental ill health in a group of devout Christians from the ethnic majority population in secular Sweden: a qualitative study
Authors: Lilja Aina , DeMarinis Valerie , Lehti Arja , Forssén Annika 
Published: October 2016

ObjectiveTo explore existential meaning-making in an ethnic-majority subgroup with mental ill health and to increase knowledge about the importance of gaining access to such information in mental healthcare.DesignQualitative study using in-depth interviews and systematic text condensation analysis.Participants17 devote Christians with an ethnic-Swedish background, 12 women and 5 men, 30–73 years old, from different congregations across Sweden, having sought medical care for mental ill health of any kind.SettingThe secular Swedish society.ResultsA living, although asymmetric, relationship with God often was seen as the most important relationship, giving hope and support when ill, but creating feelings of abandonment and fear if perceived as threatened. Symptoms were interpreted through an existential framework influenced by their view of God. A perceived judging God increased feelings of guilt, sinfulness and shame. A perceived merciful God soothed symptoms and promoted recovery. Existential consequences, such as being unable to pray or participate in congregational rituals, caused feelings of ‘spiritual homelessness’. Participants gave biopsychosocial explanations of their mental ill health, consonant with and sometimes painfully conflicting with existential explanations, such as being attacked by demons. Three different patterns of interaction among biopsychosocial and existential dimensions in their explanatory systems of illness causation were identified: (a) comprehensive thinking and consensus; (b) division and parallel functions and (c) division and competitive functions.ConclusionsPrevailing medical models for understanding mental ill health do not include the individual's existential experiences, which are important for identifying risk and protective factors as well as possible resources for recovery. The various expressions of existential meaning-making identified in this devout religious subgroup illustrate that existential information cannot be generalised, even within a small, seemingly homogenous group. The three identified patterns of interactions formed a typology that may be of use in clinical settings.
Impact of service redesign on the socioeconomic inequity in revascularisation rates for patients with acute myocardial infarction: a natural experiment and electronic record-linked cohort study
Authors: Evans Lloyd W , van Woerden Hugo , Davies Gareth R , Fone David 
Published: October 2016

AimTo investigate the impact of service redesign in the provision of revascularisation procedures on the historical socioeconomic inequity in revascularisation rates for patients with acute myocardial infarction (AMI).DesignNatural experiment and retrospective cohort study using linked data sets in the Secure Anonymised Information Linkage databank.Non-randomised interventionAn increase in the capacity of revascularisation procedures and service redesign in the provision of revascularisation in late 2011 to early 2012.SettingSouth Wales cardiac network, Census 2011 population 1 359 051 aged 35 years and over.Participants9128 participants admitted to an NHS hospital with a first AMI between 1 January 2010 and 30 June 2013, with 6-months follow-up.Main outcome measureHazard ratios (HRs) for the time to revascularisation for deprivation quintiles, age, gender, comorbidities, rural–urban classification and revascularisation facilities of admitting hospital.ResultsIn the preintervention period, there was a statistically significant decreased adjusted risk of revascularisation for participants in the most deprived quintile compared to the least deprived quintile (HR 0.80; 95% CI 0.69 to 0.92, p=0.002). In the postintervention period, the increase in revascularisation rates was statistically significant in all quintiles, and there was no longer any statistically significant difference in the adjusted revascularisation risk between the most and the least deprived quintile (HR 1.04; 95% CI 0.89 to 1.20, p<0.649). However, inequity persisted for those aged 75 years and over (HR 0.40; 95% CI 0.35 to 0.46, p<0.001) and women (HR 0.77; 95% CI 0.70 to 0.86, p<0.001).ConclusionsSocioeconomic inequity of access to revascularisation was no longer apparent following redesign of revascularisation services in the south Wales cardiac network, although inequity persisted for women and those aged 75+ years. Increasing the capacity of revascularisation did not differentially benefit participants from the least deprived areas.
Desensitisation to cigarette package graphic health warnings: a cohort comparison between London and Singapore
Authors: Ratneswaran Culadeeban , Chisnall Ben , Li Mingyue , Tan Sarah , Douiri Abdel , Anantham Devanand , Steier Joerg 
Published: October 2016

ObjectivesWe compared 2 sociocultural cohorts with different duration of exposure to graphic health warning labels (GHWL), to investigate a possible desensitisation to their use. We further studied how a differing awareness and emotional impact of smoking-associated risks could be used to prevent this.SettingStructured interviews of patients from the general respiratory department were undertaken between 2012 and 2013 in 2 tertiary hospitals in Singapore and London.Participants266 participants were studied, 163 Londoners (35% smokers, 54% male, age 52±18 years) and 103 Singaporeans (53% smokers, p=0.003; 78% male, p<0.001; age 58±15 years, p=0.012).Main outcomes and measures50 items assessed demographics, smoking history, knowledge and the deterring impact of smoking-associated risks. After showing 10 GHWL, the impact on emotional response, cognitive processing and intended smoking behaviour was recorded.ResultsSingaporeans scored lower than the Londoners across all label processing constructs, and this was consistent for the smoking and non-smoking groups. Londoners experienced more ‘disgust’ and felt GHWL were more effective at preventing initiation of, or quitting, smoking. Singaporeans had a lower awareness of lung cancer (82% vs 96%, p<0.001), despite ranking it as the most deterring consequence of smoking. Overall, ‘blindness’ was the least known potential risk (28%), despite being ranked as more deterring than ‘stroke’ and ‘oral cancer’ in all participants.ConclusionsThe length of exposure to GHWL impacts on the effectiveness. However, acknowledging the different levels of awareness and emotional impact of smoking-associated risks within different sociocultural cohorts could be used to maintain their impact.
Primary care interventions and current service innovations in modifying long-term outcomes after stroke: a protocol for a scoping review
Authors: Pindus Dominika M , Lim Lisa , Rundell A Viona , Hobbs Victoria , Aziz Noorazah Abd , Mullis Ricky , Mant Jonathan 
Published: October 2016

IntroductionInterventions delivered by primary and/or community care have the potential to reach the majority of stroke survivors and carers and offer ongoing support. However, an integrative account emerging from the reviews of interventions addressing specific long-term outcomes after stroke is lacking. The aims of the proposed scoping review are to provide an overview of: (1) primary care and community healthcare interventions by generalist healthcare professionals to stroke survivors and/or their informal carers to address long-term outcomes after stroke, (2) the scope and characteristics of interventions which were successful in addressing long-term outcomes, and (3) developments in current clinical practice.Methods and analysisStudies that focused on adult community dwelling stroke survivors and informal carers were included. Academic electronic databases will be searched to identify reviews of randomised controlled trials (RCTs) and controlled trials, trials from the past 5 years; reviews of observational studies. Practice exemplars from grey literature will be identified through advanced Google search. Reports, guidelines and other documents of major health organisations, clinical professional bodies, and stroke charities in the UK and internationally will be included. Two reviewers will independently screen titles, abstracts and full texts for inclusion of published literature. One reviewer will screen search results from the grey literature and identify relevant documents for inclusion. Data synthesis will include analysis of the number, type of studies, year and country of publication, a summary of intervention components/service or practice, outcomes addressed, main results (an indicator of effectiveness) and a description of included interventions.Ethics and disseminationThe review will help identify components of care and care pathways for primary care services for stroke. By comparing the results with stroke survivors' and carers' needs identified in the literature, the review will highlight potential gaps in research and practice relevant to long-term care after stroke.