bluuebunny/crossref_metadata_2025_split huggingface dataset:
Force-Induced Strengthening of the Interaction between
Staphylococcus aureus
Clumping Factor B and Loricrin
Authors: Vitry Pauline , Valotteau Claire , Feuillie Cécile , Bernard Simon , Alsteens David , Geoghegan Joan A. , Dufrêne Yves F. 
Published: December 2017

ABSTRACT

Bacterial pathogens that colonize host surfaces are subjected to physical stresses such as fluid flow and cell surface contacts. How bacteria respond to such mechanical cues is an important yet poorly understood issue.
Staphylococcus aureus
uses a repertoire of surface proteins to resist shear stress during the colonization of host tissues, but whether their adhesive functions can be modulated by physical forces is not known. Here, we show that the interaction of
S. aureus
clumping factor B (ClfB) with the squamous epithelial cell envelope protein loricrin is enhanced by mechanical force. We find that ClfB mediates
S. aureus
adhesion to loricrin through weak and strong molecular interactions both in a laboratory strain and in a clinical isolate. Strong forces (~1,500 pN), among the strongest measured for a receptor-ligand bond, are consistent with a high-affinity “dock, lock, and latch” binding mechanism involving dynamic conformational changes in the adhesin. Notably, we demonstrate that the strength of the ClfB-loricrin bond increases as mechanical force is applied. These findings favor a two-state model whereby bacterial adhesion to loricrin is enhanced through force-induced conformational changes in the ClfB molecule, from a weakly binding folded state to a strongly binding extended state. This force-sensitive mechanism may provide
S. aureus
with a means to finely tune its adhesive properties during the colonization of host surfaces, helping cells to attach firmly under high shear stress and to detach and spread under low shear stress.

IMPORTANCE
Staphylococcus aureus
colonizes the human skin and the nose and can cause various disorders, including superficial skin lesions and invasive infections. During nasal colonization, the
S. aureus
surface protein clumping factor B (ClfB) binds to the squamous epithelial cell envelope protein loricrin, but the molecular interactions involved are poorly understood. Here, we unravel the molecular mechanism guiding the ClfB-loricrin interaction. We show that the ClfB-loricrin bond is remarkably strong, consistent with a high-affinity “dock, lock, and latch” binding mechanism. We discover that the ClfB-loricrin interaction is enhanced under tensile loading, thus providing evidence that the function of an
S. aureus
surface protein can be activated by physical stress.
PCR detection of segmented filamentous bacteria in the terminal ileum of patients with ulcerative colitis
Authors: Finotti Alessia , Gasparello Jessica , Lampronti Ilaria , Cosenza Lucia Carmela , Maconi Giovanni , Matarese Vincenzo , Gentili Valentina , Di Luca Dario , Gambari Roberto , Caselli Michele 
Published: December 2017

ObjectivesSegmented filamentous bacteria (SFB) have been detected in a wide range of different animal. Recently, the presence of SFB-like bacteria was shown in biopsies of the terminal ileum and ileocecal valve of both patients with ulcerative colitis and control subjects. The aim of this study was to verify whether PCR methods could be used for the detection of SFB in biopsy of patients with ulcerative colitis and its relationships with the disease stage.MethodsPCR methods were used to identify SFB in biopsies from the terminal ileum of patients with ulcerative colitis, showing that this approach represents a useful tool for the detection of SFB presence and analysis of the bacterial load.ResultsOur analysis detected SFB in all faecal samples of children at the time of weaning, and also show that putative SFB sequences are present in both patients with ulcerative colitis and control subjects. Results obtained using real-time quantitative PCR analysis confirm the presence of putative SFB sequences in samples from the terminal ileum of patients with ulcerative colitis and in control subjects.ConclusionsThe presence of putative SFB sequence in both patients with ulcerative colitis and control subject suggests that SFB cannot be considered as being uniquely associated with the disease. The second conclusion is that among the patients with ulcerative colitis, a tendency does exist for active disease samples to show higher SFB load, opening new perspectives about possible identification and pharmacological manipulation of SFB-mediated processes for new therapeutic strategy.
Association between individual and neighbourhood socioeconomic factors and masticatory efficiency: a cross-sectional analysis of the Paris Prospective Study 3
Authors: Boillot Adrien , Jouven Xavier , Rangé Hélène , Perier Marie Cécile , Thomas Frédérique , Guibout Catherine , Pannier Bruno , Boutouyrie Pierre , Empana Jean-Philippe , Bouchard Philippe 
Published: December 2017

BackgroundThere is a lack of evidence on the impact of socioeconomic factors on masticatory efficiency. The present study investigates the relationship between individual and neighbourhood socioeconomic factors (main exposure) and the number of masticatory units (MUs) used as surrogate of the masticatory efficiency (main outcome).MethodsIn this cross-sectional study nested in the Paris Prospective Study 3, 4270 adults aged 50–75 and recruited from 13 June 2008 to 31 May 2012 underwent a full-mouth examination. Number of MUs defined as pairs of opposing teeth or dental prostheses allowing mastication, number of missing teeth and gingival inflammation were documented. The individual component of the socioeconomic status was evaluated with an individual multidimensional deprivation score and education level. The neighbourhood component of the socioeconomic status was evaluated with the FDep99 deprivation index. Associations were quantified using marginal models.ResultsIn multivariate analyses, having less than 5 MUs was associated with (1) the most deprived neighbourhoods (OR=2.27 (95% CI 1.63 to 3.17)), (2) less than 12 years of educational attainment (OR=2.20 (95% CI 1.66 to 2.92)) and (3) the highest individual score of deprivation (OR=3.23 (95% CI 2.24 to 4.65)). Associations with education and individual score of deprivation were consistent across the level of neighbourhood deprivation. Comparable associations were observed with the number of missing teeth. Associations with gingival inflammation were of lower magnitude; the relationship was present for deprivation markers but not for education.ConclusionPoor masticatory efficiency is associated with low educational attainment and high deprivation scores.
Modelling the implications of reducing smoking prevalence: the benefits of increasing the UK tobacco duty escalator to public health and economic outcomes
Authors: Knuchel-Takano Andre , Hunt Daniel , Jaccard Abbygail , Bhimjiyani Arti , Brown Martin , Retat Lise , Brown Katrina , Hinde Sebastian , Selvarajah Chit , Bauld Linda , Webber Laura 
Published: December 2017

IntroductionTaxing tobacco is one of the most effective ways to reduce smoking prevalence, mitigate its devastating consequential health harms and progress towards a tobacco-free society. This study modelled the health and economic impacts of increasing the existing cigarette tobacco duty escalator (TDE) in the UK from the current 2% above consumer price inflation to 5%.MethodsA two-stage modelling process was used. First, a non-linear multivariate regression model was fitted to cross-sectional smoking data, creating longitudinal projections from 2015 to 2035. Second, these projections were used to predict the future incidence, prevalence and cost of 17 smoking-related diseases using a Monte Carlo microsimulation approach. A sustained increase in the duty escalator was evaluated against a baseline of continuing historical smoking trends and the existing duty escalator.ResultsA sustained increase in the TDE is projected to reduce adult smoking prevalence to 6% in 2035, from 10% in a baseline scenario. After increasing the TDE, only 65% of female and 60% of male would-be smokers would actually be smoking in 2035. The intervention is projected to avoid around 75 200 new cases of smoking-related diseases between 2015 and 2035. In 2035 alone, £49 m in National Health Service and social care costs and £192 m in societal premature mortality and morbidity costs are projected to be avoided.ConclusionIncreasing the UK TDE to 5% above inflation could effectively reduce smoking prevalence, prevent diseases and avoid healthcare costs. It would deliver substantial progress towards a tobacco-free society and should be implemented by the UK Government with urgency.
lncRNA MIAT promotes proliferation and invasion of HCC cells via sponging miR-214
Authors: Huang Xinli , Gao Yun , Qin Jianjie , Lu Sen 
Published: December 2017

The aberrant expression of long noncoding RNAs (lncRNAs) has been involved in various human tumors including hepatocellular carcinoma (HCC). Our study aimed to investigate the potential molecular mechanism of lncRNA myocardial infarction-associated transcript (MIAT) in HCC. The expression of MIAT and micro-RNA (miR)-214 in HCC tissues and cells was examined by quantitative real-time PCR, and the levels of enhancer of zeste homolog 2 (EZH2) and β-catenin were detected by Western blot assay. Immunoprecipitation analysis was used to detect the level of H3/H4 histone acetylation. RNA pull-down assay was performed to confirm the targeting regulatory relationship between miR-214 and MIAT. Cell viability, proliferation, and invasion were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), [3H]thymidine incorporation, and Transwell assays, respectively. BALB/c nude mice were used to establish a hepatocellular carcinoma animal model with subcutaneous injection of SK-HEP-1 cells. Upregulation of MIAT is related to the proliferation and invasion of HCC, and downregulating MIAT expression inhibited HCC cell proliferation and invasion. The H3/H4 histone acetylation level of MIAT promoter in HCC tissues was higher than that in normal tissues. MIAT negatively regulated miR-214 in HCC cells. Inhibition of miR-214 reversed the influence of MIAT downregulation on HCC cell proliferation and invasion. In nude mouse xenograft models, downregulation of MIAT markedly suppressed the tumor growth of HCC via releasing miR-214. In conclusion, lncRNA MIAT promotes the proliferation and invasion of HCC cells through sponging miR-214, which brings a novel target for the therapy and prognosis of hepatocellular carcinoma. NEW & NOTEWORTHY This is the first research showing long noncoding RNA (lncRNA) myocardial infarction-associated transcript (MIAT) to have a regulatory effect on hepatocellular carcinoma. Micro-RNA (miR)-214 could be sponged by MIAT to promote the proliferation and invasion of hepatocellular carcinoma cells. The lncRNA MIAT/miR-214 axis brings a novel insight for the therapy and prognosis of hepatocellular carcinoma.
Reduced longitudinal contraction is associated with ischemic mitral regurgitation after posterior MI
Authors: Ishikawa Kiyotake , Watanabe Shin , Hammoudi Nadjib , Aguero Jaume , Bikou Olympia , Fish Kenneth , Hajjar Roger J. 
Published: December 2017

The role of left ventricular (LV) longitudinal contraction in ischemic mitral regurgitation (MR) remains unclear. We hypothesized that reduced longitudinal contraction disrupts normal mitral valve plane displacement during systole and leads to mitral valve tethering, thereby inducing ischemic MR. Twenty-three Yorkshire pigs underwent induction of different-sized posterior myocardial infarction (MI) using a percutaneous approach. The incidence of MR and its association with LV longitudinal strain were examined using speckle-tracking echocardiography at 1 mo post-MI to determine their relationship. A total of 17 pigs survived MI and completed the study. Pigs developed no more than mild MR after proximal left circumflex artery (LCx) occlusion (LCx group; n = 7). Addition of a first diagonal branch (D1) occlusion to LCx-MI (LCx + D1 group; n = 7) resulted in moderate to severe MR development 1 mo post-MI. LCx + D1 animals had lower longitudinal strain compared with the LCx group, whereas circumferential strain and LV rotation did not differ significantly. Posterolateral annular displacement toward the apex was significantly reduced in LCx + D1 animals, whereas the septal annular displacement was similar, suggesting an asymmetric mitral annular plane excursion in the LCx + D1 group. To exclude the contribution of papillary muscle infarction in MR development in our model, three pigs underwent obtuse marginal branch + D1 occlusion. None of these pigs developed significant MR after 1 mo. In conclusion, reduced longitudinal contraction contributes to the development of ischemic MR in a large posterior MI. NEW & NOTEWORTHY In this study, using our unique swine models of different-sized myocardial infarction, we showed, for the first time, that reduced longitudinal contraction contributes to the development of ischemic mitral regurgitation in a large posterior myocardial infarction. Our study adds new insights into the mechanisms of ischemic mitral regurgitation pathophysiology.
Differential effects of alcohol and its metabolite acetaldehyde on vascular smooth muscle cell Notch signaling and growth
Authors: Hatch Ekaterina , Morrow David , Liu Weimin , Cahill Paul A. , Redmond Eileen M. 
Published: December 2017

Alcohol (EtOH) consumption can variously affect cardiovascular disease. Our aim was to compare the effects of EtOH and its primary metabolite acetaldehyde (ACT) on vascular smooth muscle Notch signaling and cell growth, which are important for atherogenesis. Human coronary artery smooth muscle cells (HCASMCs) were treated with EtOH (25 mM) or ACT (10 or 25 μM). As previously reported, EtOH inhibited Notch signaling and growth of HCASMCs. In contrast, ACT treatment stimulated HCASMC proliferation (cell counts) and increased proliferating cell nuclear antigen expression, concomitant with stimulation of Notch signaling, as determined by increased Notch receptor (N1 and N3) and target gene (Hairy-related transcription factor 1–3) mRNA levels. Interaction of the ligand with the Notch receptor initiates proteolytic cleavage by α- and γ-secretase, resulting in the release of the active Notch intracellular domain. Neither EtOH nor ACT had any significant effect on α-secretase activity. A fluorogenic peptide cleavage assay demonstrated almost complete inhibition by EtOH of Delta-like ligand 4-stimulated γ-secretase activity in solubilized HCASMCs (similar to the effect of the control inhibitor DAPT) but no effect of ACT treatment. EtOH, but not ACT, affected the association and distribution of the γ-secretase catalytic subunit presenilin-1 with lipid rafts, as determined by dual fluorescent labeling and confocal microscopic visualization. In conclusion, ACT stimulates vascular smooth muscle cell Notch signaling and growth, effects opposite to those of EtOH. These differential actions on vascular smooth muscle cells of EtOH and its metabolite ACT may be important in mediating the ultimate effects of drinking on cardiovascular disease. NEW & NOTEWORTHY Acetaldehyde stimulates, in a Notch-dependent manner, the vascular smooth muscle cell growth that contributes to atherogenesis; effects opposite to those of ethanol. These data suggest that in addition to ethanol itself, its metabolite acetaldehyde may also mediate some of the effects of alcohol consumption on vascular cells and, thus, cardiovascular health.
Influence of age and gender on the phase and strength of the relation between heart period and systolic blood pressure spontaneous fluctuations
Authors: Milan-Mattos Juliana C. , Porta Alberto , Perseguini Natália M. , Minatel Vinicius , Rehder-Santos Patricia , Takahashi Anielle C. M. , Mattiello Stela M. , Catai Aparecida M. 
Published: December 2017

Aging affects baroreflex regulation. The effect of senescence on baroreflex control was assessed from spontaneous fluctuations of heart period (HP) and systolic arterial pressure (SAP) through the HP-SAP gain, while the HP-SAP phase and strength are usually disregarded. This study checks whether the HP-SAP phase and strength, as estimated, respectively, via the phase of the HP-SAP cross spectrum (PhHP-SAP) and squared coherence function (K2HP-SAP), vary with age in healthy individuals and trends are gender-dependent. We evaluated 110 healthy volunteers (55 males) divided into five age subgroups (21–30, 31–40, 41–50, 51–60, and 61–70 yr). Each subgroup was formed by 22 subjects (11 males). HP series was extracted from electrocardiogram and SAP from finger arterial pressure at supine resting (REST) and during active standing (STAND). PhHP-SAP and K2HP-SAP functions were sampled in low-frequency (LF, from 0.04 to 0.15 Hz) and in high-frequency (HF, above 0.15 Hz) bands. Both at REST and during STAND PhHP-SAP(LF) showed a negative correlation with age regardless of gender even though values were more negative in women. This trend was shown to be compatible with a progressive increase of the baroreflex latency with age. At REST K2HP-SAP(LF) decreased with age regardless of gender, but during STAND the high values of K2HP-SAP(LF) were more preserved in men than women. At REST and during STAND the association of PhHP-SAP(HF) and K2HP-SAP(HF) with age was absent. The findings points to a greater instability of baroreflex control with age that seems to affect to a greater extent women than men. NEW & NOTEWORTHY Aging increases cardiac baroreflex latency and decreases the degree of cardiac baroreflex involvement in regulating cardiovascular variables. These trends are gender independent but lead to longer delays and asmaller degree of cardiac baroreflex involvement in women than in men, especially during active standing, with important implications on the tolerance to an orthostatic stressor.
Tamoxifen Resistance in Breast Cancer Is Regulated by the EZH2–ERα–GREB1 Transcriptional Axis
Authors: Wu Yanming , Zhang Zhao , Cenciarini Mauro E. , Proietti Cecilia J. , Amasino Matias , Hong Tao , Yang Mei , Liao Yiji , Chiang Huai-Chin , Kaklamani Virginia G. , Jeselsohn Rinath , Vadlamudi Ratna K. , Huang Tim Hui-Ming , Li Rong , De Angelis Carmine , Fu Xiaoyong , Elizalde Patricia V. , Schiff Rachel , Brown Myles , Xu Kexin 
Published: December 2017

Abstract
Resistance to cancer treatment can be driven by epigenetic reprogramming of specific transcriptomes in favor of the refractory phenotypes. Here we discover that tamoxifen resistance in breast cancer is driven by a regulatory axis consisting of a master transcription factor, its cofactor, and an epigenetic regulator. The oncogenic histone methyltransferase EZH2 conferred tamoxifen resistance by silencing the expression of the estrogen receptor α (ERα) cofactor GREB1. In clinical specimens, induction of DNA methylation of a particular CpG-enriched region at the GREB1 promoter negatively correlated with GREB1 levels and cell sensitivity to endocrine agents. GREB1 also ensured proper cellular reactions to different ligands by recruiting distinct sets of ERα cofactors to cis-regulatory elements, which explains the contradictory biological effects of GREB1 on breast cancer cell growth in response to estrogen or antiestrogen. In refractory cells, EZH2-dependent repression of GREB1 triggered chromatin reallocation of ERα coregulators, converting the antiestrogen into an agonist. In clinical specimens from patients receiving adjuvant tamoxifen treatment, expression levels of EZH2 and GREB1 were correlated negatively, and taken together better predicted patient responses to endocrine therapy. Overall, our work suggests a new strategy to overcome endocrine resistance in metastatic breast cancer by targeting a particular epigenetic program.
Significance: This study suggests a new strategy to overcome endocrine resistance in metastatic breast cancer by targeting a particular epigenetic program defined within. Cancer Res; 78(3); 671–84. ©2017 AACR.
The Mechanism and Representation of Korean Three-Way Phonation Contrast: External Photoglottography, Intra-Oral Air Pressure, Airflow, and Acoustic Data
Authors: Kim Hyunsoon , Maeda Shinji , Honda Kiyoshi , Crevier-Buchman Lise 
Published: December 2017

Abstract
This paper aims to refine our understanding of the speech mechanism and laryngeal features involved in the Korean lenis (/p t k/), aspirated (/ph th kh/), and fortis (/p' t' k'/) plosives. For this purpose we made measurements using a new noninvasive technique called external lighting and sensing photoglottography (ePGG) as well as intra-oral air pressure (Pio) above the glottis, airflow, and acoustic data. From simultaneous recordings of the experimental data, we were ableto quantify the laryngeal-oral coordination of glottal opening and a consonant release, and the covariance of airflow peak and duration of aspiration with glottal opening. The phasing of glottal opening and the 3-way phonation contrast occurs in the order, from early to late, fortis, lenis < aspirated plosives, and the glottal opening peak ranges from low to high in the same order. We also found that a Pio peak, the durations of a high Pio plateau and an oral closure, and F0 are independent of the glottal opening mechanism, varying in the order lenis < aspirated and fortis plosives. From these findings, we propose that the 2 independent patterns are accounted for by the articulator-based features [±spread glottis] and [±tense], respectively.
Genetic Variants Contributing to Circulating Matrix Metalloproteinase 8 Levels and Their Association With Cardiovascular Diseases
Authors: Salminen Aino , Vlachopoulou Efthymia , Havulinna Aki S. , Tervahartiala Taina , Sattler Wolfgang , Lokki Marja-Liisa , Nieminen Markku S. , Perola Markus , Salomaa Veikko , Sinisalo Juha , Meri Seppo , Sorsa Timo , Pussinen Pirkko J. 
Published: December 2017

Background—
Matrix metalloproteinase 8 (MMP-8) is a proinflammatory enzyme expressed mainly by neutrophils. Elevated serum and plasma concentrations of MMP-8 are associated with the risk for and outcome of cardiovascular diseases (CVDs). The origin of circulating MMP-8 is not completely clear.

Methods and Results—

We performed a genome-wide association study of serum MMP-8 levels in 2 populations comprising altogether 6049 individuals. Moreover, we studied whether MMP-8–associated variants are linked to increased risk of CVDs and overall mortality in >20 000 subjects. The strongest association with serum MMP-8 was found in locus 1q31.3, containing the gene for complement factor H (lead single nucleotide polymorphism: rs800292;
P
=2.4×10
–35
). In functional experiments, activation of the alternative pathway of complement in the carriers of rs800292 minor allele (Ile62 in factor H) led to decreased release of MMP-8 from neutrophils compared with the major allele (Val62 in factor H). Another association was detected in 1q21.3, containing genes
S100A8
,
S100A9
, and
S100A12
(strongest association: rs1560833;
P
=5.3×10
–15
). The minor allele of rs1560833 was inversely associated with CVD (odds ratio [95% confidence interval]: 0.90 [0.82–0.99];
P
=0.032) and the time to incident CVD event (hazard ratio [95% confidence interval]: 0.91 [0.84–0.99];
P
=0.032) in men but not in women.

Conclusions—

According to our results, the activation of the alternative pathway of the complement system strongly contributes to serum MMP-8 concentration. Genetic polymorphism in
S100A9–S100A12–S100A8
locus affects serum and plasma MMP-8 and shows a suggestive association with the risk of CVDs. Our results show that genetic variation determines a significant portion of circulating MMP-8 concentrations.