bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Intracellular Peptidyl-Prolyl
cis
/
trans
Isomerase Is Required for Folding and Activity of the Staphylococcus aureus Secreted Virulence Factor Nuclease
Authors: Wiemels Richard E. , Cech Stephanie M. , Meyer Nikki M. , Burke Caleb A. , Weiss Andy , Parks Anastacia R. , Shaw Lindsey N. , Carroll Ronan K. 
Published: October 2016

ABSTRACT

Staphylococcus aureus
is an important human pathogen that relies on a large repertoire of secreted and cell wall-associated proteins for pathogenesis. Consequently, the ability of the organism to cause disease is absolutely dependent on its ability to synthesize and successfully secrete these proteins. In this study, we investigate the role of peptidyl-prolyl
cis/trans
isomerases (PPIases) on the activity of the
S. aureus
secreted virulence factor nuclease (Nuc). We identify a staphylococcal cyclophilin-type PPIase (PpiB) that is required for optimal activity of Nuc. Disruption of
ppiB
results in decreased nuclease activity in culture supernatants; however, the levels of Nuc protein are not altered, suggesting that the decrease in activity results from misfolding of Nuc in the absence of PpiB. We go on to demonstrate that PpiB exhibits PPIase activity
in vitro
, is localized to the bacterial cytosol, and directly interacts with Nuc
in vitro
to accelerate the rate of Nuc refolding. Finally, we demonstrate an additional role for PpiB in
S. aureus
hemolysis and demonstrate that the
S. aureus
parvulin-type PPIase PrsA also plays a role in the activity of secreted virulence factors. The deletion of
prsA
leads to a decrease in secreted protease and phospholipase activity, similar to that observed in other Gram-positive pathogens. Together, these results demonstrate, for the first time to our knowledge, that PPIases play an important role in the secretion of virulence factors in
S. aureus
.

IMPORTANCE
Staphylococcus aureus
is a highly dangerous bacterial pathogen capable of causing a variety of infections throughout the human body. The ability of
S. aureus
to cause disease is largely due to an extensive repertoire of secreted and cell wall-associated proteins, including adhesins, toxins, exoenzymes, and superantigens. These virulence factors, once produced, are typically transported across the cell membrane by the secretory (Sec) system in a denatured state. Consequently, once outside the cell, they must refold into their active form. This step often requires the assistance of bacterial folding proteins, such as PPIases. In this work, we investigate the role of PPIases in
S. aureus
and uncover a cyclophilin-type enzyme that assists in the folding/refolding of staphylococcal nuclease.
SecA Cotranslationally Interacts with Nascent Substrate Proteins
In Vivo
Authors: Huber Damon , Jamshad Mohammed , Hanmer Ruby , Schibich Daniela , Döring Kristina , Marcomini Isabella , Kramer Günter , Bukau Bernd 
Published: October 2016

ABSTRACT

SecA is an essential component of the Sec machinery in bacteria, which is responsible for transporting proteins across the cytoplasmic membrane. Recent work from our laboratory indicates that SecA binds to ribosomes. Here, we used two different approaches to demonstrate that SecA also interacts with nascent polypeptides
in vivo
and that these polypeptides are Sec substrates. First, we photo-cross-linked SecA to ribosomes
in vivo
and identified mRNAs that copurify with SecA. Microarray analysis of the copurifying mRNAs indicated a strong enrichment for proteins containing Sec-targeting sequences. Second, we used a 2-dimensional (2-D) gel approach to analyze radioactively labeled nascent polypeptides that copurify with SecA, including maltose binding protein, a well-characterized SecA substrate. The interaction of SecA with nascent chains was not strongly affected in cells lacking SecB or trigger factor, both of which also interact with nascent Sec substrates. Indeed, the ability of SecB to interact with nascent chains was disrupted in strains in which the interaction between SecA and the ribosome was defective. Analysis of the interaction of SecA with purified ribosomes containing arrested nascent chains
in vitro
indicates that SecA can begin to interact with a variety of nascent chains when they reach a length of ∼110 amino acids, which is considerably shorter than the length required for interaction with SecB. Our results suggest that SecA cotranslationally recognizes nascent Sec substrates and that this recognition could be required for the efficient delivery of these proteins to the membrane-embedded Sec machinery.

IMPORTANCE
SecA is an ATPase that provides the energy for the translocation of proteins across the cytoplasmic membrane by the Sec machinery in bacteria. The translocation of most of these proteins is uncoupled from protein synthesis and is frequently described as “posttranslational.” Here, we show that SecA interacts with nascent Sec substrates. This interaction is not dependent on SecB or trigger factor, which also interact with nascent Sec substrates. Moreover, the interaction of SecB with nascent polypeptides is dependent on the interaction of SecA with the ribosome, suggesting that interaction of the nascent chain with SecA precedes interaction with SecB. Our results suggest that SecA could recognize substrate proteins cotranslationally in order to efficiently target them for uncoupled protein translocation.
Retinal microvascular network geometry and cognitive abilities in community-dwelling older people: The Lothian Birth Cohort 1936 study
Authors: McGrory Sarah , Taylor Adele M , Kirin Mirna , Corley Janie , Pattie Alison , Cox Simon R , Dhillon Baljean , Wardlaw Joanna M , Doubal Fergus N , Starr John M , Trucco Emanuele , MacGillivray Thomas J , Deary Ian J 
Published: October 2016

AimTo examine the relationship between retinal vascular morphology and cognitive abilities in a narrow-age cohort of community-dwelling older people.MethodsDigital retinal images taken at age ∼73 years from 683 participants of the Lothian Birth Cohort 1936 (LBC1936) were analysed with Singapore I Vessel Assessment (SIVA) software. Multiple regression models were applied to determine cross-sectional associations between retinal vascular parameters and general cognitive ability (g), memory, processing speed, visuospatial ability, crystallised cognitive ability and change in IQ from childhood to older age.ResultsAfter adjustment for cognitive ability at age 11 years and cardiovascular risk factors, venular length-to-diameter ratio was nominally significantly associated with processing speed (β=−0.116, p=0.01) andg(β=−0.079, p=0.04). Arteriolar length-to-diameter ratio was associated with visuospatial ability (β=0.092, p=0.04). Decreased arteriolar junctional exponent deviation and increased arteriolar branching coefficient values were associated with less relative decline in IQ between childhood and older age (arteriolar junctional exponent deviation: β=−0.101, p=0.02; arteriolar branching coefficient: β=0.089, p=0.04). Data are presented as standardised β coefficients (β) reflecting change in cognitive domain score associated with an increase of 1 SD unit in retinal parameter. None of these nominally significant associations remained significant after correction for multiple statistical testing.ConclusionsRetinal parameters contributed <1% of the variance in the majority of associations observed. Whereas retinal analysis may have potential for early detection of some types of age-related cognitive decline and dementia, our results present little evidence that retinal vascular features are associated with non-pathological cognitive ageing.
ULTRASOUND MEASUREMENT OF CHEST WALL THICKNESS IN ELITE RUGBY PLAYERS; A COMPARISON BETWEEN THE NEEDLE THORACOCENTESIS SITES
Authors: Jones C , Adejuwon A 
Published: October 2016

AimsThere are no known published studies to support current pitch side guidelines for the management of a tension pneumothorax in a sporting population (1). Temporary management of this condition involves needle thoracocentesis (NT) at the 2nd intercostal space mid clavicular line (2MCL). The 5th intercostal space anterior axillary line (5AAL) has been suggested as an alternative site.1 The aim of the study was to compare chest wall thickness (CWT) at the 2MCL and the 5AAL of an elite rugby union team. The secondary aim was to calculate potential NT failure between player positions; Forwards and Backs.MethodsPotential failure was calculated by comparing CWT in relation to both a standard cannula length of 4.5 cm and the advised needle length of 5.0 cm. Ultrasound recorded three measurements of CWT at the 2MCL and 5AAL on both sides of the thorax.ResultsForty-three male players with a mean age of 25.7 years participated. Forwards demonstrated a thicker CWT than Backs at both sites. The mean CWT at 2MCL was 3.78 cm in Forwards and 3.30 cm in Backs. The mean CWT at the 5AAL site was uniformly thinner and measured 3.16 cm in Forwards and 2.40 cm in Backs. 22.2% (n=6) of Forwards had a CWT greater then 4.5 cm. 11.1% (n=3) of Forwards had a CWT greater then 5.0 cm at 2MCL. For all player positions the CWT at the 5AAL was less than 5.0 cm.ConclusionsForward position rugby players had a greater CWT than Back players. One in ten Forward players had the potential to fail NT in accordance to suggested guidelines. CWT at the 5AAL was significantly thinner (p<0.05) than at the 2MCL for all players and may be a more suitable NT site for Forward players.
Temporal and long-term trend analysis of class C notifiable diseases in China from 2009 to 2014
Authors: Zhang Xingyu , Hou Fengsu , Qiao Zhijiao , Li Xiaosong , Zhou Lijun , Liu Yuanyuan , Zhang Tao 
Published: October 2016

ObjectivesTime series models are effective tools for disease forecasting. This study aims to explore the time series behaviour of 11 notifiable diseases in China and to predict their incidence through effective models.Settings and participantsThe Chinese Ministry of Health started to publish class C notifiable diseases in 2009. The monthly reported case time series of 11 infectious diseases from the surveillance system between 2009 and 2014 was collected.MethodsWe performed a descriptive and a time series study using the surveillance data. Decomposition methods were used to explore (1) their seasonality expressed in the form of seasonal indices and (2) their long-term trend in the form of a linear regression model. Autoregressive integrated moving average (ARIMA) models have been established for each disease.ResultsThe number of cases and deaths caused by hand, foot and mouth disease ranks number 1 among the detected diseases. It occurred most often in May and July and increased, on average, by 0.14126/100 000 per month. The remaining incidence models show good fit except the influenza and hydatid disease models. Both the hydatid disease and influenza series become white noise after differencing, so no available ARIMA model can be fitted for these two diseases.ConclusionTime series analysis of effective surveillance time series is useful for better understanding the occurrence of the 11 types of infectious disease.
Associations between excessive adiposity and seroprevalence of herpes simplex virus type 1 and type 2 among US adults: a population-based age–period–cohort analysis
Authors: Liu Su-Hsun , Tzeng I-Shiang , Hsieh Tsung-Han , Huang Yhu-Chering 
Published: October 2016

ObjectivesEvidence on the association between herpes simplex virus (HSV) and excessive adiposity, such as obesity (body mass index ≥30 kg/m2) and abdominal obesity (waist circumference (WC) >102 or 88 cm), has been inconsistent. We sought to examine whether age–period–cohort (APC) effects could explain for the observed heterogeneities.DesignPopulation-based cross-sectional study.ParticipantsAdults aged 20–49 years with available serological data in the National Health and Nutrition Examination Survey (NHANES) in 1999–2012.Exposure measuresObesity and abdominal obesity.ResultsIn men, excessive adiposity was generally not associated with HSV1 or HSV2 (all p>0.05); however, there were positive correlations between HSV seroprevalence and excessive adiposity in certain age and birth cohort groups. Based on APC analysis, abdominally obese men aged 30–40 years showed a nearly 20% increase in risk for HSV1 seropositivity (adjusted prevalence ratio (aPR)=1.18; 95% CI 1.10 to 1.27) as compared with abdominally non-obese men of the same age; there was no such association in men of other age groups. Also, men of a large WC who were born before 1962 or after 1979 had a 28% higher risk for HSV2 seropositivity than those of a normal WC in the same birth cohorts (aPR=1.28, 95% CI 1.17 to 1.54); yet the association did not hold for men in other cohorts (aPR=0.86, 95% CI 0.64 to 1.17). In women, a large WC was correlated with a minimally increased HSV1 seroprevalence (aPR=1.07, 95% CI 1.01 to 1.13) but not with HSV2 seropositivity (aPR=1.13; 95% CI 0.99 to 1.28). Likewise, there were strong associations between abdominal obesity and HSV2 seropositivity in subgroups of women participating in the earliest survey cycle (aPR=1.41, 95% CI 1.12 to 1.78) but not in other survey periods (aPR=0.94, 95% CI 0.85 to 1.03).ConclusionsThere was no consistent evidence for strong associations between HSV seropositivity and excessive adiposity in adults. APC analysis results further cautioned the generalisability of previous reports based on 1 or 2 cycles of survey data.
Text2PreventCVD: protocol for a systematic review and individual participant data meta-analysis of text message-based interventions for the prevention of cardiovascular diseases
Authors: Chow Clara K , Islam Sheikh Mohammed Shariful , Farmer Andrew , Bobrow Kirsty , Maddision Ralph , Whittaker Robyn , Dale Leila Pfaeffli , Lechner Andreas , Niessen Louis , Lear Scott A , Eapen Zubin J , Santo Karla , Stepien Sandrine , Redfern Julie , Rodgers Anthony 
Published: October 2016

IntroductionText message interventions have been shown to be effective in prevention and management of several non-communicable disease risk factors. However, the extent to which their effects might vary in different participants and settings is uncertain. We aim to conduct a systematic review and individual participant data (IPD) meta-analysis of randomised clinical trials examining text message interventions aimed to prevent cardiovascular diseases (CVD) through modification of cardiovascular risk factors (CVRFs).Methods and analysisSystematic review and IPD meta-analysis will be conducted according to Preferred Reporting Items for Systematic review and Meta-Analysis of IPD (PRISMA-IPD) guidelines. Electronic database of published studies (MEDLINE, EMBASE, PsycINFO and Cochrane Library) and international trial registries will be searched to identify relevant randomised clinical trials. Authors of studies meeting the inclusion criteria will be invited to join the IPD meta-analysis group and contribute study data to the common database. The primary outcome will be the difference between intervention and control groups in blood pressure at 6-month follow-up. Key secondary outcomes include effects on lipid parameters, body mass index, smoking levels and self-reported quality of life. If sufficient data is available, we will also analyse blood pressure and other secondary outcomes at 12 months. IPD meta-analysis will be performed using a one-step approach and modelling data simultaneously while accounting for the clustering of the participants within studies. This study will use the existing data to assess the effectiveness of text message-based interventions on CVRFs, the consistency of any effects by participant subgroups and across different healthcare settings.Ethics and disseminationEthical approval was obtained for the individual studies by the trial investigators from relevant local ethics committees. This study will include anonymised data for secondary analysis and investigators will be asked to check that this is consistent with their existing approvals. Results will be disseminated via scientific forums including peer-reviewed publications and presentations at international conferences.Trial registration numberCRD42016033236.
Genomic Heterogeneity and Exceptional Response to Dual Pathway Inhibition in Anaplastic Thyroid Cancer
Authors: Gibson William J. , Ruan Daniel T. , Paulson Vera A. , Barletta Justine A. , Hanna Glenn J. , Kraft Stefan , Calles Antonio , Nehs Matthew A. , Moore Francis D. , Taylor-Weiner Amaro , Wala Jeremiah A. , Zack Travis I. , Lee Thomas C. , Fennessy Fiona M. , Alexander Erik K. , Thomas Tom , Janne Pasi A. , Garraway Levi A. , Carter Scott L. , Beroukhim Rameen , Lorch Jochen H. , Van Allen Eliezer M. 
Published: October 2016

Abstract
Purpose: Cancers may resist single-agent targeted therapies when the flux of cellular growth signals is shifted from one pathway to another. Blockade of multiple pathways may be necessary for effective inhibition of tumor growth. We document a case in which a patient with anaplastic thyroid carcinoma (ATC) failed to respond to either mTOR/PI3K or combined RAF/MEK inhibition but experienced a dramatic response when both drug regimens were combined.
Experimental Design: Multi-region whole-exome sequencing of five diagnostic and four autopsy tumor biopsies was performed. Meta-analysis of DNA and RNA sequencing studies of ATC was performed.
Results: Sequencing revealed truncal BRAF and PIK3CA mutations, which are known to activate the MAPK and PI3K/AKT pathways, respectively. Meta-analysis demonstrated 10.3% cooccurrence of MAPK and PI3K pathway alterations in ATC. These tumors display a separate transcriptional profile from other ATCs, consistent with a novel subgroup of ATC.
Conclusions: BRAF and PIK3CA mutations define a distinct subset of ATC. Blockade of the MAPK and PI3K pathways appears necessary for tumor response in this subset of ATC. This identification of synergistic activity between targeted agents may inform clinical trial design in ATC. Clin Cancer Res; 23(9); 2367–73. ©2016 AACR.
Assessment of the European Society of Cardiology 0-Hour/1-Hour Algorithm to Rule-Out and Rule-In Acute Myocardial Infarction
Authors: Pickering John W. , Greenslade Jaimi H. , Cullen Louise , Flaws Dylan , Parsonage William , Aldous Sally , George Peter , Worster Andrew , Kavsak Peter A. , Than Martin P. 
Published: October 2016

Background:
The new European Society of Cardiology guidelines to rule-in and rule-out acute myocardial infarction (AMI) in the emergency department include a rapid assessment algorithm based on high-sensitivity cardiac troponin and sampling at 0 and 1 hour. Emergency department physicians require high sensitivity to confidently rule-out AMI, whereas cardiologists aim to minimize false-positive results.

Methods:
High-sensitivity troponin I and T assays were used to measure troponin concentrations in patients presenting with chest-pain symptoms and being investigated for possible acute coronary syndrome at hospitals in New Zealand, Australia, and Canada. AMI outcomes were independently adjudicated by at least 2 physicians. The European Society of Cardiology algorithm performance with each assay was assessed by the sensitivity and proportion with AMI ruled out and the positive predictive value and proportion ruled-in.

Results:
There were 2222 patients with serial high-sensitivity troponin T and high-sensitivity troponin I measurements. The high-sensitivity troponin T algorithm ruled out 1425 (64.1%) with a sensitivity of 97.1% (95% confidence interval [CI], 94.0%–98.8%) and ruled-in 292 (13.1%) with a positive predictive value of 63.4% (95% CI, 57.5%–68.9%).
The high-sensitivity troponin I algorithm ruled out 1205 (54.2%) with a sensitivity of 98.8% (95% CI, 96.4%–99.7%)) and ruled-in 310 (14.0%) with a positive predictive value of 68.1% (95% CI, 62.6%–73.2%).

Conclusions:
The sensitivity of the European Society of Cardiology rapid assessment 0-/1-hour algorithm to rule-out AMI with high-sensitivity troponin may be insufficient for some emergency department physicians to confidently send patients home. These algorithms may prove useful to identify patients requiring expedited management. However, the positive predictive value was modest for both algorithms.
Macrophage Foam Cell–Derived Extracellular Vesicles Promote Vascular Smooth Muscle Cell Migration and Adhesion
Authors: Niu Chenguang , Wang Xu , Zhao Mingming , Cai Tanxi , Liu Peibin , Li Jizhao , Willard Belinda , Zu Lingyun , Zhou Enchen , Li Yufeng , Pan Bing , Yang Fuquan , Zheng Lemin 
Published: October 2016

Background
A new mechanism for intercellular communication has recently emerged that involves intercellular transfer of extracellular vesicles (EVs). Several studies have indicated that EVs may play a potential role in cell‐to‐cell communication between macrophage foam cells and vascular smooth muscle cells (VSMCs) in atherosclerotic lesion.

Methods and Results
This study involved the comparison of circulating EVs from atherosclerotic patients and control participants. The results showed that the circulation of the patients contained more leukocyte‐derived EVs and that these EVs promoted more VSMC adhesion and migration than those of healthy participants. We then established a macrophage foam cell model and characterized the EVs from the macrophages. We used flow cytometric analyses and cell migration and adhesion assays and determined that the foam cells generated more EVs than the normal macrophages and that the foam cell–derived EVs were capable of promoting increased levels of VSMC migration and adhesion. Furthermore, we performed a proteomic analysis of the EVs. The data showed that the foam cell–derived EVs may promote VSMC adhesion and migration by regulating the actin cytoskeleton and focal adhesion pathways. In addition, Western blotting revealed that foam cell–derived EVs could promote the phosphorylation of ERK and Akt in VSMCs in a time‐dependent manner. We also found that foam cell–derived EVs could enter the VSMCs and transfer integrins to the surface of these cells.

Conclusions
The data in our present study provide the first evidence that EVs from foam cells could promote VSMC migration and adhesion, which may be mediated by the integration of EVs into VSMCs and the subsequent downstream activation of ERK and Akt.
Barotropic and Baroclinic Eddy Feedbacks in the Midlatitude Jet Variability and Responses to Climate Change–Like Thermal Forcings
Authors: Burrows D. Alex , Chen Gang , Sun Lantao 
Published: October 2016

Abstract
Studies have suggested that the persistence in the meridional vacillation of the midlatitude jet (i.e., annular mode time scale) in comprehensive climate models is related to the model biases in climatological jet latitude, with important implications for projections of future climates and midlatitude weather events. Through the use of the recently developed finite-amplitude wave activity formalism and feedback quantifying techniques, this paper has quantified the role of barotropic and baroclinic eddy feedbacks in annular mode time scales using an idealized dry atmospheric model.
The eddy–mean flow interaction that characterizes the persistent anomalous state of the midlatitude jet depends on processes associated with the lower-tropospheric source of vertically propagating Rossby waves, baroclinic mechanisms, and processes associated with upper-tropospheric wave propagation and breaking, barotropic mechanisms. A variety of climate change–like thermal forcings are used to generate a range of meridional shifts in the midlatitude eddy-driven jet. The idealized model shows a reduction in annular mode time scale associated with an increase in jet latitude, similar to comprehensive climate models. This decrease in time scale can be attributed to a similar decrease in the strength of the barotropic eddy feedback, which, in the positive phase of the annular mode, is characterized by anomalous potential vorticity (PV) mixing on the equatorward flank of the climatological jet. The decrease in subtropical PV mixing is, in turn, associated with a stronger subtropical jet as the eddy-driven jet is more distant from the subtropics. These results highlight the importance of subtropical eddy–mean flow interactions for the persistence of an eddy-driven jet.